apoER2 (apolipoprotein E receptor-2) is a transmembrane receptor in the low-density lipoprotein receptor (LDLR) family with unique tissue expression. A single-nucleotide polymorphism that encodes the R952Q sequence variant has been associated with elevated plasma cholesterol levels and increased myocardial infarction risk in humans. The objective of this study was to delineate the mechanism underlying the association between the apoER2 R952Q variant and increased atherosclerosis risk.

In-stent restenosis is characterized by a significant reduction in lumen diameter within the stented segment, primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia. PFN1 (profilin-1), an actin-sequestering protein extensively studied in amyotrophic lateral sclerosis, remains less explored in neointimal hyperplasia.

PC (protein C) is a plasma anticoagulant encoded by ; mutation in both alleles results in neonatal purpura fulminans-a fatal systemic thrombotic disorder. In the present study, we aimed to develop a genome editing treatment to cure congenital PC deficiency.

Lymphangiogenesis is believed to be a protective response in the setting of multiple forms of kidney injury and mitigates the progression of interstitial fibrosis. To augment this protective response, promoting kidney lymphangiogenesis is being investigated as a potential treatment to slow the progression of kidney disease. As injury-related lymphangiogenesis is driven by signaling from the receptor VEGFR3 (vascular endothelial growth factor receptor 3) in response to the cognate growth factor VEGF (vascular endothelial growth factor)-C released by tubular epithelial cells, this signaling pathway is a candidate for future kidney therapeutics. However, the consequences to kidney development and function to targeting this signaling pathway remain poorly defined.

Atherosclerosis affects patients with systemic immune-mediated inflammatory diseases at an increased rate compared with the general population. In recent years, our understanding of the pathophysiology of atherosclerosis has advanced considerably. Nevertheless, cardiovascular imaging modalities that can adequately assess the biological background of atherosclerosis have not reached widespread clinical adoption. Novel developments in cardiac imaging have the potential to enhance the diagnostic yield of these modalities further while providing essential insights into the anatomy, composition, and biology of atherosclerotic lesions. In this review, we highlight some of the latest developments in the field for the evaluation of atherosclerosis using advances in echocardiography, computed tomography, positron emission tomography, and cardiovascular magnetic resonance. Additionally, we discuss evidence specifically in patients with immune-mediated inflammatory diseases and outline unmet research needs for future development.

Vascular inflammation is a hallmark of both primary systemic vasculitis and atherosclerosis. As such, cardiovascular events are common in patients with vasculitis and likely due to both direct vascular inflammation and accelerated atherosclerosis. Direct cardiac involvement is possible in all vasculitides, though more commonly described in Takayasu arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis. Accelerated atherosclerosis has been described in Takayasu arteritis and antineutrophil cytoplasmic antibody-associated vasculitis, though there remains a paucity of data in other forms of vasculitis. Multiple screening and management approaches for cardiovascular risk in people with vasculitis have been proposed, though evidence-based guidelines are lacking. In this review, we discuss the latest evidence in epidemiology, mechanisms, and screening for atherosclerosis in patients with primary systemic vasculitides.

Andexanet alfa (andexanet) is the only Food and Drug Administration-approved antidote for direct FXa (factor Xa) inhibitors but has been reported to cause resistance to unfractionated heparin (UFH). This has delayed anticoagulation for procedures requiring cardiopulmonary bypass. The mechanism, andexanet and UFH dose dependence, and thrombotic risk of andexanet-associated heparin resistance are unknown.

Cerebral cavernous malformation (CCM) is a disease characterized by vascular malformations that primarily develop in the brain. These malformations are prone to leak, and their rupture or thrombotic closure can cause life-threatening hemorrhages and strokes. Mouse models have been instrumental to study the disease, but most cause premature lethality, precluding the investigation of disease mechanisms through intravital microscopy. Current mouse models also do not recapitulate human CCM skin lesions.

The development of aortic dissection (AD) is closely associated with inflammation. The Trem2 (triggering receptor expressed on myeloid cells 2)/Tyrobp (TYRO protein tyrosine kinase-binding protein) signaling pathway critically regulates innate immunity and has emerged as an important target in cardiovascular diseases; however, its role in AD remains unclear.

Pharmacological inhibition of megalin (also known as LRP2 [low-density lipoprotein receptor-related protein-2]) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PTCs), the purpose of this study was to determine whether PTC-specific deletion of megalin reduces hypercholesterolemia-induced atherosclerosis in mice.

The pancreatic vasculature displays tissue-specific physiological and functional adaptations that support rapid insulin response by β-cells. However, the digestive enzymes have made it difficult to characterize pancreatic endothelial cells (ECs), resulting in the poor understanding of pancreatic EC specialization.

Radiation therapy (RT) is a cornerstone in cancer treatment (used in 50% of cases), yet challenges persist because damage to normal tissue through direct impact of radiation or bystander effects is inevitable. Injury of macrovessels by RT manifests as obstructive disease, which is akin to atherosclerotic disease. Historically observed in coronary arteries of patients treated for breast cancer and lymphoma, it also affects patients receiving contemporary therapy for lung and chest cancers. Moreover, radiation at various sites can lead to peripheral vascular disease. An aspect of radiation-induced injury that has received little attention is microvascular injury, which typically results from damage to the endothelium and is considered the primary driver of RT-induced toxicity in the skin, kidney, and brain. This review delves into the clinical manifestations of RT-induced vascular disease, signaling pathways, cellular targets affected by radiation injury, and preclinical models of RT-induced vascular injury. The goal is to inspire the development of innovative strategies to prevent RT-related cardiovascular disease.

Chronic kidney disease confers a high risk of atherosclerotic cardiovascular disease (ASCVD), partly due to hyperlipidemia. Although statins reduce the risk of ASCVD in chronic kidney disease, residual risk persists. We investigated whether higher remnant cholesterol is associated with an increased risk of ASCVD in statin users and nonusers with impaired renal function.

Individuals with autoimmune inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, are at increased risk for cardiovascular disease. While these diseases share common features of systemic inflammation, the impact of individual autoimmune inflammatory conditions on circulating lipids and lipoproteins varies by specific disease, disease activity, and the immune-suppressing medications used to treat these conditions. A common feature observed in many autoimmune inflammatory diseases is the development of a proatherogenic dyslipidemic state, characterized by dysfunctional HDLs (high-density lipoproteins) and increased oxidation of LDLs (low-density lipoproteins). Various disease-modifying antirheumatic drugs also have complex and variable effects on lipids, and it is critical to take this into consideration when evaluating lipid-related risk in individuals with immune-mediated inflammatory conditions. This review aims to critically evaluate the current understanding of the relationship between immune-mediated inflammatory diseases and dyslipidemia, the underlying mechanisms contributing to atherogenesis, and the impact of various pharmacotherapies on lipid profiles and cardiovascular risk. We also discuss the role of lipid-lowering therapies, particularly statins, in managing residual risk in this high-risk population and explore the potential of emerging therapies with complementary anti-inflammatory and lipid-lowering effects.

Positive remodeling (PR) is an atherosclerotic plaque feature defined as an increase in arterial caliber at the level of an atheroma, in response to increasing plaque burden. The mechanisms that lead to its formation are incompletely understood, but its role in coronary atherosclerosis has major clinical implications. Indeed, plaques with PR have elevated risk of provoking acute cardiac events. Hence, PR figures among the high-risk plaque features that cardiac imaging studies should report. This review aims to provide an overview of the current literature on coronary PR. It outlines the pathophysiology of PR, the different techniques used to assess its presence, and the imaging findings associated to PR, on both noninvasive and invasive studies. This review also summarizes clinical observations, trials, and studies, focused on the impact of PR on clinical outcome.

he proportion of time a patient’s international normalized ratio remains within a therapeutic range (TTR) is critical for the efficacy and safety of vitamin K antagonist anticoagulant therapy (warfarin or acenocumarol). Poor-quality vitamin K antagonist therapy, as measured by TTR, can cause thrombotic and bleeding complications. TTR is affected by age, body mass index, genetics, comorbidities, and medications. The gut microbiota influences the host metabolism and could indirectly affect medication metabolism or anticoagulant absorption, potentially impacting TTR. A recent review reported that microbial metabolites, vitamin K–producing bacteria, and structural modifications of vitamin K antagonist molecules may indirectly alter vitamin K antagonist medication availability. High taxonomic resolution, functional profiling, and detection of novel microorganisms are possible with shotgun metagenome sequencing. In this pilot cross-sectional study of warfarin-treated individuals, we examine the relationship between gut metagenome composition and TTR.

Vascular leakage is a deadly complication of severe infections, ranging from bacterial sepsis to malaria. Worldwide, septicemia is among the top 10 causes of lethality because of the shock and multiorgan dysfunction that arise from the host vascular response. In the monoclonal gammopathy-associated capillary leak syndrome (MG-CLS), even otherwise mundane infections induce recurrent septic-like episodes of profound microvascular hyperpermeability and shock. There are no defined genetic risk factors for MG-CLS or effective treatments for acute crises.