Cancer patients may encounter the onset of cardiovascular disease due to tumor advancement or chemotherapy, commonly known as "cardiotoxicity." In this respect, the conventional chemotherapy treatment protocol involves a mixture of different medications. These medications can be detrimental to cardiac tissue, consequently exposing the patient to the possibility of irreversible cardiac injury. The enhancement of oxidative stress and inflammation is an important mechanism of chemotherapeutic agents for developing cardiotoxicity. Regarding their dual pro- and anti-inflammatory functions, platelets can significantly influence the progression or suppression of cardiotoxicity. Therefore, the expression of platelet activatory markers can serve as valuable prognostic indicators for cardiotoxicity. The primary objective of this study is to examine the significance of platelets in cardiotoxicity and explore potential strategies that could effectively target malignant cells while minimizing their cytotoxic impact, such as cardiotoxicity and thrombosis.

The Hippo-yes-associated protein (YAP) signaling pathway plays a crucial role in cell proliferation, differentiation, and death. It is known to have impact on the progression and development of cardiovascular diseases (CVDs) as well as in the regeneration of cardiomyocytes (CMs). However, further research is needed to understand the molecular mechanisms by which the Hippo-YAP pathway affects the pathological processes of CVDs in order to evaluate its potential clinical applications. In this review, we have summarized the recent findings on the role of the Hippo-YAP pathway in CVDs such as myocardial infarction, heart failure, and cardiomyopathy, as well as its in CM development. This review calls attention to the potential roles of the Hippo-YAP pathway as a relevant target for the future treatment of CVDs.

Inhalation of ambient particulate matter (PM) and ozone (O) has been associated with increased cardiovascular morbidity and mortality. However, the interactive effects of PM and O on cardiac dysfunction and disease have not been thoroughly examined, especially at a proteomic level. The purpose of this study was to identify and compare proteome changes in spontaneously hypertensive (SH) rats co-exposed to concentrated ambient particulates (CAPs) and O, with a focus on investigating inflammatory and metabolic pathways, which are the two major ones implicated in the pathophysiology of cardiac dysfunction. For this, we measured and compared changes in expression status of 9 critical pro- and anti-inflammatory cytokines using multiplexed ELISA and 450 metabolic proteins involved in ATP production, oxidative phosphorylation, cytoskeletal organization, and stress response using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) in cardiac tissue of SH rats exposed to CAPs alone, O alone, and CAPs + O. Proteomic expression profiling revealed that CAPs alone, O alone, and CAPs + O differentially altered protein expression patterns, and utilized divergent mechanisms to affect inflammatory and metabolic pathways and responses. Ingenuity Pathway Analysis (IPA) of the proteomic data demonstrated that the metabolic protein network centered by gap junction alpha-1 protein (GJA 1) was interconnected with the inflammatory cytokine network centered by nuclear factor kappa beta (NF-kB) potentially suggesting inflammation-induced alterations in metabolic pathways, or vice versa, collectively contributing to the development of cardiac dysfunction in response to CAPs and O exposure. These findings may enhance understanding of the pathophysiology of cardiac dysfunction induced by air pollution and provide testable hypotheses regarding mechanisms of action.

(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway.

Cardiac magnetic resonance (CMR) enables the assessment of tissue characteristics of the myocardium. Changes in the extracellular volume (ECV) and fibrosis volume (FV) of the myocardium are sensitive and early pathogenetic markers and have prognostic significance. The aim of the study was to assess ECV and FV of left ventricular myocardium in T1 mapping sequence in patients with a history of SARS-CoV-2 infection, considering vaccination status against COVID-19. The study group consisted of 97 patients (52.54 ± 8.31 years, 53% women and 47% men). The participants were divided into three subgroups: A) patients with a history of symptomatic SARS-CoV-2 infection, unvaccinated against COVID-19 (n = 39), B) patients with a history of symptomatic SARS-CoV-2 infection, with a full vaccination schedule against COVID-19 (n = 22), and C) persons without a history of SARS-CoV-2 infection constituting the control subgroup (C, n = 36). All patients underwent 1.5 T cardiac magnetic resonance. In subgroup A compared to subgroups B and C, both the ECV whole myocardium and ECV segments 2, 5-6, 8, and 10-11 were statistically significantly higher. In addition, the ECV segment 16 was statistically significantly higher in subgroup A than in subgroup C. Also, the FV whole myocardium was statistically significantly higher in subgroup A in comparison to subgroups B and C. There were no significant differences in ECV and FV between subgroups B and C. In summary, unvaccinated against COVID-19 patients with a history of symptomatic SARS-CoV-2 infection have higher myocardial ECV and FV values in the T1 mapping sequence, compared to those without COVID-19 and those suffering from COVID-19, previously vaccinated with the full vaccination schedule.

Viral myocarditis (VMC) is an inflammatory disease of the myocardium caused by cardioviral infection, especially coxsackievirus B3 (CVB3), and is a major contributor to acute heart failure and sudden cardiac death in children and adolescents. LncRNA MALAT1 knockdown reportedly inhibits the differentiation of Th17 cells to attenuate CVB3-induced VMC in mice. Moreover, long non-coding RNAs (lncRNAs) interact with RNA-binding proteins (RBPs) to regulate UPF1-mediated mRNA decay. However, it remains unclear whether MALAT1 can bind to UPF1 to mediate the mRNA decay of its target genes in VMC. Herein, we aimed to explore the effect of lncRNA MALAT1 on UPF1-mediated SIRT6 mRNA decay in VMC using in vivo and in vitro experiments. CVB3-infected BABL/C mice were used as VMC models, and MALAT1 interfering adenovirus was injected to achieve MALAT1 knockdown. The heart function of the VMC mice was assessed using echocardiography. Pathological changes in myocardial tissues were assessed after hematoxylin-eosin staining. Myocardial injury and inflammation were evaluated by measuring creatine kinase isoenzyme B, cardiac troponin T, interleukin (IL)-1β, and IL-18. TUNEL staining was performed to assess apoptosis in myocardial tissues. In vitro experiments were performed using H9c2 cells after transfection and CVB3 infection. The lactic dehydrogenase release, caspase-1 activity, and IL-1β and IL-18 levels in the cellular supernatant were detected. Western blotting was performed to determine the expression of pyroptosis-related proteins (GSDMD-N, NLRP3, ASC, and Cleaved-Caspase-1) and Wnt/β-catenin signal pathway-related proteins (Wnt1, β-catenin, and p-GSK-3β). RNA immunoprecipitation and RNA stability assays assessed the relationship between MALAT1, UPF1, and SIRT6. CVB3-infected mice and H9c2 cells exhibited elevated MALAT1 and reduced SIRT6 expression. MALAT1 knockdown or SIRT6 overexpression suppressed inflammation and pyroptosis and inhibited the activation of the Wnt/β-catenin signal pathway in myocardial tissues and cells. MALAT1 enhanced the enrichment of SIRT6 mRNA by UPF1 and disturbed the stability of SIRT6 mRNA to promote the development of VMC. MALAT1 can bind UPF1 to mediate SIRT6 mRNA decay and activate the Wnt/β-catenin signal pathway in VMC.

Myocardial infarction (MI) is a lethal cardiovascular disease worldwide. Emerging evidence has revealed the critical role of gut dysbiosis and impaired gut-brain axis in the pathological progression of MI. Tanshinone IIA (Tan IIA), a traditional Chinese medicine, has been demonstrated to exert therapeutic effects for MI. However, the effects of Tan IIA on gut-brain communication and its potential mechanisms post-MI are still unclear. In this study, we initially found that Tan IIA significantly reduced myocardial inflammation, apoptosis and fibrosis, therefore alleviating hypertrophy and improving cardiac function following MI, suggesting the cardioprotective effect of Tan IIA against MI. Additionally, we observed that Tan IIA improved the gut microbiota as evidenced by changing the α-diversity and β-diversity, and reduced histopathological impairments by decreasing inflammation and permeability in the intestinal tissues, indicating the substantial improvement of Tan IIA in gut function post-MI. Lastly, Tan IIA notably reduced lipopolysaccharides (LPS) level in serum, inflammation responses in paraventricular nucleus (PVN) and sympathetic hyperexcitability following MI, suggesting that restoration of Tan IIA on MI-induced brain alterations. Collectively, these results indicated that the cardioprotective effects of Tan IIA against MI might be associated with improvement in gut-brain axis, and LPS might be the critical factor linking gut and brain. Mechanically, Tan IIA-induced decreased intestinal damage reduced LPS release into serum, and reduced serum LPS contributes to decreased neuroinflammation with PVN and sympathetic inactivation, therefore protecting the myocardium against MI-induced injury.

Previous observational studies have explored the association between serum lipids, apolipoproteins, and adverse ventricular/aortic structure and function. However, whether a causal link exists is uncertain. This study employed a two-sample Mendelian randomization (MR), colocalization, reverse, and multivariable MR (MVMR) approach to examine the causal associations among five serum lipids, two apolipoproteins, and 32 cardiac magnetic resonance (CMR) traits. Utilizing single-nucleotide polymorphisms (SNPs) linked to serum lipids and apolipoproteins as instrumental variables. CMR traits from seven independent genome-wide association studies served as preclinical endophenotypes, offering insights into aortic and cardiac structure/function. The primary analysis utilized a random-effects inverse variance method (IVW), followed by sensitivity and validation analyses. In the primary IVW MR analyses, genetically predicted low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with increased descending aorta strain (DAo strain) (β = 0.098; P = 2.69E-07) and ascending aorta strain (AAo strain) (β = 0.079; P = 5.19E-05). Genetically predicted high-density lipoprotein cholesterol (HDL-C) levels were positively correlated with left ventricular radial peak diastolic strain rate (LV-PDSRll) (β = 0.176; P = 2.89E-05) and the left ventricular longitudinal peak diastolic strain rate (LV-PDSRrr) (β = 0.059; P = 2.44E-06), and negatively correlated with left ventricular regional wall thickness (LVRWT). While apolipoprotein B (ApoB) levels were positively correlated with AAo strain (β = 0.076; P = 1.16E-05), DAo strain (β = 0.065; P = 2.77E-05). A shared causal variant was identified to demonstrate the associations of ApoB with AAo strain and DAo strain using colocalization analysis. Sensitivity analyses confirmed the robustness of these associations. Targeting lipid and apolipoprotein levels through interventions may provide novel strategies for the primary prevention of CVDs.

Doxorubicin (Dox) is a commonly used chemotherapy drug effective against a range of cancers, but its clinical application is greatly limited by dose-dependent and cumulative cardiotoxicity. Mitochondrial dysfunction is recognized as a key factor in Dox-induced cardiotoxicity, leading to oxidative stress, disrupted calcium balance, and activation of apoptotic pathways. Recent research has emphasized the potential of small molecules that specifically target mitochondria to alleviate these harmful effects. This review provides a comprehensive analysis of small molecules that offer cardioprotection by preserving mitochondrial function in the context of doxorubicin-induced cardiotoxicity (DIC). The mechanisms of action include the reduction of reactive oxygen species (ROS) production, stabilization of mitochondrial membrane potential, enhancement of mitochondrial biogenesis, and modulation of key signaling pathways involved in cell survival and apoptosis. By targeting mitochondria, these small molecules present a promising therapeutic strategy to prevent or reduce the cardiotoxic effects associated with Dox treatment. This review not only discusses the mechanistic actions of these agents but also emphasizes their potential in improving cardiovascular outcomes for cancer patients. Gaining insight into these mechanisms can help in creating more effective strategies to safeguard the heart during chemotherapy, allowing for the ongoing use of Dox with a lower risk to the patient's cardiovascular health. This review highlights the critical role of mitochondria-targeted therapies as a promising approach in addressing DIC.

Diabetic cardiomyopathy (DCM) is a common and severe complication of Diabetes mellitus (DM). Dapagliflozin (DAPA) is an oral anti-diabetic drug worldwide for the treatment of type 2 DM. However, the action and mechanism of DAPA in cardiac fibrosis during DCM remain vague. Primary cardiac fibroblasts (CFs) were incubated with high glucose (HG) in vitro. Cell proliferation was detected by MTT and EdU assays. Oxidative stress was evaluated by determining the production of reactive oxygen species and malondialdehyde. Cell fibrosis was assessed by detecting fibrosis-related proteins by western blotting. Levels of Mettl3 (Methyltransferase 3) and Marcks (myristoylated alanine-rich C kinase substrate) were measured using qRT-PCR and western blotting. The m6A modification profile was determined by methylated RNA immunoprecipitation assay and the interaction between Mettl3 and Marcks was verified using dual-luciferase reporter and RIP assays. DAPA treatment alleviated HG-induced proliferation, oxidative stress, and fibrosis in CFs. HG promoted the expression of Mettl3 in CFs. Knockdown of Mettl3 reversed HG-induced proliferation, oxidative stress, and fibrosis in CFs; moreover, forced expression of Mettl3 abolished the protective effects of DAPA on CFs under HG condition. Mechanistically, Mettl3 interacted with Marcks in CFs and induced Marcks mRNA m6A modification. HG induced high expression of Marcks in CFs. The overexpression of Marcks could counteract DAPA or Mettl3 knockdown-evoked inhibitory effects on CF proliferation, oxidative stress, and fibrosis under HG condition. Dapagliflozin suppressed HG-induced proliferation, oxidative stress, and fibrosis by reducing Mettl3-induced m6A modification in Marcks mRNA.

The role of ferroptosis, an iron-dependent lipid peroxidation regulated cell death pathway, remains obscure during myocardial infarction (MI) recovery. Our study aims to clarify ferroptosis' function in post-MI cardiac recovery, explore the consequences of iron overload and ferroptosis for myocardial remodeling, and assess the effects of Liproxstatin-1 (Lipro-1) treatment on macrophage functionality. Moreover, we examine the potential of Astaxanthin (ASTX), recognized for its antioxidative properties, to mitigate ferroptosis during MI recovery and its subsequent ramifications for myocardial remodeling. Our results demonstrate persistent ferroptosis during MI recovery, marked by decreased Glutathione Peroxidase 4 and increased Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) and Ferroportin 1 alongside elevated lipid peroxidation and iron levels up to D21. We identified a significant correlation between ferroptosis and macrophage activity, noted by the increase in macrophage populations co-expressing GPX4 and ACSL4 markers in the peri-infarct area by D21. Liproxstatin-1 treatment reduced macrophage (CD68 +) counts, promoted M2 polarization decreased inflammation, and improved cardiac function. Myocardial remodeling was improved in Lipro-1-treated rats, as shown by decreased fibrosis and reduced levels of α-SMA, Collagen I, and Collagen III proteins. ASTX treatment also exhibited an inhibiting effect on ferroptosis indicators, and encouraged M2 macrophage polarization, reduced inflammation, and enhanced both cardiac function and myocardial remodeling, mirroring the beneficial effects observed with Lipro-1. In summary, the interactions between ferroptosis, macrophage polarization, and myocardial remodeling are crucial for cardiac function improvement post-MI. Lipro-1 and ASTX emerge as promising therapeutic agents by modulating post-MI ferroptosis and related immune responses.

Histone demethylation in cardiac hypertrophy is poorly understood. This study aims to determine the role of the histone demethylase LSD1 in pathological cardiac hypertrophy. Both isoprenaline (ISO)-treated and transverse aortic constriction (TAC)-treated rats developed hypertrophic hearts. LSD1 was significantly decreased; the histone marks mono- and dimethyl H3K4 and H3K9 (H3K4me1/2 and H3K9me1/2) were significantly up-regulated in the hypertrophic heart tissue, as well as the expression of the ANP, α-HMC and MLV-2v genes. An LSD1 inhibitor, OG-L002 could also induce cardiac hypertrophy and enhance the induction of cardiac hypertrophy by ISO. Overexpressed LSD1 abolished ISO-induced cardiac hypertrophy and downregulated H3K4me1/2 and H3K9me1/2 expression. Overexpression of LSD1 also reduced the expression of ANP, α-HMC and MLV-2v. In addition, we have reported isoprenaline (ISO) as one of the histone demethylase LSD1 inhibitors. This was confirmed by molecular docking, molecular dynamic studies and a histone demethylation assay. The H3K4me1/2 expression increases with the incubation of ISO in HEK 293T and HELA cells. CaMKII could be significantly activated by the LSD1 inhibitor OG-L002 as well as by ISO in rats. In summary, we have identified a novel role for LSD1 in initiating and maintaining cardiac hypertrophy.

With the increasing of PI3K/AKT/mTOR (PAM) inhibitors in cancer therapy, there is a growing need to understand the incidence of cardiovascular events (CVAEs) associated with PAM inhibitors. A systematic search of all randomized clinical trials (RCTs) containing at least one PAM group in electronic databases such as PubMed, ClinicalTrials.gov registry, Embase, Medline, Cochrane Library, and major conferences was performed to extract available CVAEs. The cut-off date was January 31, 2024. Study heterogeneity was assessed using the I statistic. The risk of CVAEs associated with PAM inhibitors was calculated using Peto OR. The primary outcome was the incidence (95% CI) of PAM inhibitors cardiovascular adverse events in the total population and subgroups. The secondary outcome was the pooled risk of different CVAEs associated with PAM inhibitor exposure in the RCTs. 33 unique RCTs (n = 12,351) were included. The incidence of PAM inhibitors CVAEs of any grade in the intervention group was 48.2%, yielding a combined OR of 2.52 (95% CI 1.82-3.49). The incidence of severe adverse cardiovascular events (≥ grade 3) in the intervention group was estimated at 7.1%, yielding a combined Peto OR of 1.41 (95% CI 1.04-1.93). PAM inhibitors were associated with an increased risk of 5 CVAEs including peripheral edema, lymphoedema, hypercholesterolemia, hypertriglyceridaemia and hyperlipidemia, with higher risks for hypercholesterolemia (Peto OR: 3.27,95% CI 2.61-4.11, P < 0.01; I = 55.5%, P = 0.06) and hyperlipidemia (Peto OR: 3.53. 95% CI 1.70-7.32, P < 0.01; I = 19.3%, P = 0.29). This study identified an overall incidence of PAM inhibitors CVAEs and the increased risks associated with PAM inhibitor for five specific CVAEs, not confined to hypercholesterolemia and peripheral edema.

In recent years, concerns have been raised regarding the safety of exposure to pyriproxyfen (PPF), a larvicide commonly used in drinking water reservoirs to control populations of disease-vector mosquitoes for human safety. These concerns are focused mainly on exposure by pregnant women, since studies have shown deleterious effects of PPF on embryonic development, mainly addressing the central nervous system. However, since previous studies showed reduced growth in embryos exposed to PPF, we hypothesize that PPF exposure impairs the cardiovascular system, responsible for ensuring appropriate blood supply, which leads to stunted growth. This study aimed to investigate the impact of PPF exposure on heart ventricular morphology, its influence on cell proliferation and apoptosis, as well as assess the impact on the functionality of the heart and on embryonic growth. Chicken embryos were used as a model and two sublethal concentrations were tested: 0.01 mg/L and 10 mg/L PPF. Thinning of cardiac tissue was evident in heart structures at 10 mg/L PPF. Furthermore, DNA double-strand breaks and reduced cell proliferation were observed, combined with decreased apoptosis suggesting cell cycle arrest, especially in the left ventricle for both concentrations. In addition, these PPF concentrations induced heart arrhythmia, although no changes in heart rate were observed. Embryos exposed to 0.01 mg/L showed reduced body and heart mass, crown-rump length, and thoracic perimeter, while head circumference was reduced in both exposed groups. Together, combining morphological, molecular, and physiological parameters, this study showed the cardiotoxic effects of PPF exposure and elucidated its impacts on embryonic growth.

The effect of low-dose ionizing radiation exposure on the risk of cardiovascular disease (CVD) represents a significant concern in the field of radiation protection. The prevailing approach to mitigating the adverse effects of low-dose or low-dose-rate radiation does not currently incorporate the potential risk of CVD, despite the possibility that such risk may be a substantial contributor to overall health hazards. Current evidence suggests a potential association between radiation exposure and CVD; however, the overall findings remain inconclusive. This is particularly due to the uncertainty surrounding the influence of significant non-radiation risk factors on the associations reported in epidemiological studies. It is difficult to discern the underlying connection in observational epidemiology when there is substantial variation in baseline risk factors. The paucity of epidemiological research in this domain is being partially offset by the advancement of multi-omics approaches. These methods assist in identifying radiosensitive targets, comprehending underlying biological processes, and pinpointing biomarkers. This, in turn, fortifies the evidence gleaned from epidemiological studies. In this review, we delve into the body of epidemiological research pertaining to CVD induced by low-dose ionizing radiation and the application of multi-omics techniques. The integration of these two methodologies holds the promise of identifying specific molecules or biological pathways that can be employed to validate endpoints related to radiation risk assessment.

The objective of this study is to determine the diagnostic utility of combining homocysteine (HCY), lipoprotein-associated phospholipase A2 (LP-PLA2), and the C-reactive protein-to-albumin ratio (CAR) for carotid atherosclerosis (CAS) and plaque stability in patients with essential hypertension (EH). A total of 280 patients with EH were divided into 2 groups according to ultrasound diagnosis: CAS (n = 106) and non-CAS (N-CAS [n = 174]). The CAS group was further segmented into plaque-stable (n = 50) and plaque non-stable (n = 56) groups. General data were collected for all patients. Risk factors associated with CAS and plaque instability in patients with EH, and the diagnostic utility of HCY, LP-PLA2, and CAR testing alone, or in combination, for assessing CAS and plaque instability were determined. Mean age, systolic blood pressure (SBP), duration of EH, smoking, total cholesterol high-density lipoprotein cholesterol, HCY, LP-PLA2 levels, and CAR were higher in the CAS group than those in the N-CAS group (P < 0.05). SBP, duration of EH, HCY and LP-PLA2 levels, and CAR were independent risk factors for CAS (P < 0.05). In addition, HCY, LP-PLA2, and CAR alone demonstrated significant diagnostic efficacy (P < 0.001) but were inferior to the combined diagnostic utility of the 3 parameters (P < 0.001). HCY and LP-PLA2 levels, and CAR were higher in the plaque non-stable than in the plaque-stable group (P < 0.05). Duration of EH, low-density lipoprotein cholesterol, HCY, LP-PLA2, and CAR independently influenced plaque instability in patients with CAS (P < 0.05). The combined diagnostic utility of HCY, LP-PLA2, and CAR (P < 0.001) was superior to that of each parameter alone and demonstrated more pronounced diagnostic efficacy (P < 0.001). HCY, LP-PLA2, and CAR were independent risk factors for CAS and plaque instability in patients with EH. HCY, LP-PLA2, and CAR demonstrated significant diagnostic efficacy for CAS and plaque instability, and combination of the 3 demonstrated the most pronounced diagnostic efficacy.

Doxorubicin (DOX) is a remarkable chemotherapeutic agent, however, its adverse effect on DOX-induced cardiotoxicity (DIC) is a rising concern. Recent research has identified carvacrol (CAR), an antioxidant and anti-inflammatory agent, as a promising natural compound for protecting against DIC. This study aims to investigate the potential cardioprotective effects properties of CAR in vitro and in vivo. The cardioprotective effect of CAR was assessed by pretreating H9c2 cells with non-toxic CAR for 24 h, followed by co-treatment with DOX (10 μM) for an additional 24 h. The cell viability was determined using an MTT assay. For the in vivo study, male Sprague-Dawley rats (200-250 g) were randomly divided into three groups: control, cardiotoxicity (DOX), and treatment (CAR + DOX) groups. CAR (50 mg/kg, BW) was administered orally to the CAR + DOX groups for 14 days. Then, a single dose of DOX (15 mg/kg/i.p, BW) was administered on day 15 for DOX and CAR + DOX groups. The rats were allowed to recover for 3 days before being sacrificed. Our results demonstrated that DOX (10 µM) significantly reduced H9c2 cell viability by 50% (p < 0.0001), and CAR (0.067 µM) protected H9c2 cells from DIC (p = 0.0045). In the rat model, CAR pretreatment effectively mitigated DOX-induced reductions in systolic pressure (p = 0.0007), pulse pressure (p = 0.0213), hypertrophy (p = 0.0049), and cardiac fibrosis (p = 0.0006). However, the pretreatment did not alter the heart function, oxidative stress, and antioxidant enzymes. In conclusion, our results indicate that CAR could potentially serve as an adjuvant to reduce cardiotoxicity by ameliorating myocardial fibrosis and hypertrophy.

The hypothalamic paraventricular nucleus (PVN), as an important integrating center, plays a prominent role in the pathogenesis of hypertension, in maintaining the stability of cardiovascular activity through peripheral sympathetic nervous activity and secretion of various humoral factors. Acknowledging that the mechanistic targets of the endocannabinoid type 1 receptor (CB1R) are the key signaling systems involved in the regulation of hypertension, we sought to clarify whether inhibition of CB1R within the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats were randomly assigned to different groups and treated with bilateral PVN injections of AM251 (CB1R antagonist, 10 µg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for four weeks. Bilateral PVN injections of AM251 significantly decreased the heart rate, the body weight and the mean arterial pressure in SHRs. AM251 lowered the expression of CB1R, Wnt3, active-β-catenin, p-IKKβ, RAS components, pro-inflammatory cytokines and elevated the expression level of Glycogen synthase kinase3β and Superoxide Dismutase in the PVN of hypertensive rats. Our findings suggest that inhibition of CB1R in the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway and broaden our current understanding of the pathological mechanism and clinical treatment of hypertension.

The advent of heated tobacco products (HTPs) has introduced new variables in the study of nicotine delivery systems and their health implications. Amidst concerns over cardiovascular effects, this study aims to elucidate the acute impact of HTP inhalation on extracellular vesicles (EV) levels in young, healthy individuals. In this controlled, acute exposure study, 23 young, healthy volunteers were subjected to HTP inhalation. EV levels of endothelial and platelet origin were quantified through flow cytometry before and after exposure. Data analysis was performed using multiple measures ANOVA to assess changes in EV concentrations. Our findings reveal a significant increase in EVs of endothelial and platelet origin following short-term HTP inhalation with nicotine. Notably, no significant change was observed in leukocyte- and neutrophil-derived EVs. This increase in EVs suggests acute vascular stress, with peak levels observed 4 h post-exposure. The rise in endothelial and platelet-derived EVs aligns with documented responses to acute vascular injury, paralleling the effects seen with traditional cigarette and e-cigarette use. Despite HTPs being marketed as safer alternatives, our results indicate that nicotine-containing HTPs may still pose significant vascular risks. These findings contribute to the growing body of evidence cautioning against the perceived safety of HTPs and reinforce the importance of regulatory oversight and public health initiatives targeting nicotine delivery technologies. Trial Registrations: ClinicalTrials.gov ID: NCT04824495, registered 2021-01-07.

Congenital heart disease (CHD) is a major cause of infant mortality and morbidity, with growing interest in the role of environmental factors in its etiology. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has been implicated in the development of CHD. This study aimed to investigate the effects of DEHP exposure on fetal heart development in mice. Pregnant mice exposed to DEHP exhibited increased fetal malformations, decreased fetal weight, and reduced crown-rump length.f Transcriptomic analysis revealed the downregulation of genes involved in aerobic respiration and mitochondrial ATP synthesis. Functional assays demonstrated reduced mitochondrial respiration, decreased ATP production, elevated reactive oxygen species levels, and lowered mitochondrial membrane potential in DEHP-exposed fetal cardiomyocytes. These findings underscore the detrimental effects of DEHP on fetal cardiac health and provide insights into the molecular mechanisms underlying DEHP-induced CHD. Understanding these mechanisms is crucial for developing preventive strategies against environmental toxicants that affect fetal cardiac development.