Low, oscillatory flow/shear patterns are associated with atherosclerotic lesion development. Increased expression of K3.1 has been found in Vascular Smooth Muscle (VSM), macrophages and T-cells in lesions from humans and mice. Increased expression of K3.1, is also required for VSM cell proliferation and migration. Previously, we showed that the specific K3.1 inhibitor, TRAM-34, could inhibit coronary neointimal development following balloon injury in swine. Atherosclerosis develops in regions with a low, oscillatory (i.e. atheroprone) flow pattern. Therefore, we used the Partial Carotid Ligation (PCL) model in high-fat fed, Apoe mice to determine the role of K3.1 in atherosclerotic lesion composition and development. PCL was performed on 8-10 week old male Apoe mice and subsequently placed on a Western diet (TD.88137, Teklad) for 4 weeks. Mice received daily s.c. injections of TRAM-34 (120 mg/kg) or equal volumes of vehicle (peanut oil, PO). 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) treatment reduced lesion size ~50% ( < 0.05). In addition, lesions from TRAM-34 treated mice contained less collagen (6% ± 1% vs. 15% ± 2%; < 0.05), fibronectin (14% ± 3% vs. 32% ± 3%; < 0.05) and smooth muscle content (19% ± 2% vs. 29% ± 3%; < 0.05). Conversely, TRAM-34 had no effect on total cholesterol (1455 vs. 1334 mg/dl, PO and TRAM, resp.) or body weight (29.1 vs. 28.8 g, PO and TRAM, resp.). Medial smooth muscle of atherosclerotic carotids showed diminished RE1-Silencing Transcription Factor (REST)/Neural Restrictive Silencing Factor (NRSF) expression, while REST overexpression inhibited smooth muscle migration. Together, these data support a downregulation of REST/NRSF and upregulation of K3.1 in determining smooth muscle and matrix content of atherosclerotic lesions.

The commonest causes of dementia are Alzheimer's disease and vascular cognitive impairment. Although these conditions have been viewed as distinct entities, there is increasing evidence that neurodegenerative and vascular pathologies interact or overlap to cause cognitive decline, and that at least in some cases individuals at risk of cognitive decline exhibit abnormal cardiovascular physiology long before emergence of disease. However, the mechanisms linking haemodynamic disturbances with cognitive impairment and the various pathologies that cause dementia are poorly understood. A sub-sample of 502 participants from the Medical Research Council National Survey of Health and Development (NSHD) have participated in the first visit of a neuroscience sub-study referred to as Insight 46, where clinical, cognitive, imaging, and lifestyle data have been collected for the purpose of elucidating the pathological changes preceding dementia. This paper outlines the cardiovascular phenotyping performed in the follow-up visit of Insight 46, with the study participants now aged 74. In addition to standard cardiovascular assessments such as blood pressure measurements, echocardiography, and electrocardiography (ECG), functional Near Infrared Spectroscopy (fNIRS) has been included to provide an assessment of cerebrovascular function. A detailed description of the fNIRS protocol along with preliminary results from pilot data is presented. The combination of lifestyle data, brain structure/function, cognitive performance, and cardiovascular health obtained not only from Insight 46, but also from the whole NSHD provides an exciting opportunity to advance our understanding of the cardiovascular mechanisms underlying dementia and cognitive decline, and identify novel targets for intervention.

Individuals with Down syndrome (DS) experience autonomic dysfunction, with reduced sympathetic and parasympathetic control. This results in alterations in resting heart rate and blood pressure and attenuated responses to sympathoexcitatory stimuli. It is unknown to what extent this impacts the regulation of peripheral blood flow in response to sympathetic stimuli, which is an important prerequisite to exercise and perform work. Therefore, we aimed to investigate differences in peripheral blood flow regulation in response to lower body negative pressure (LBNP) between individuals with and without DS.

[This corrects the article DOI: 10.1016/j.artres.2017.02.005.].

Common carotid artery (CCA) intima-media thickness (IMT), lumen diameter, and maximum plaque thickness were assessed on ultrasound images. The objective of the study was to evaluate the intra- and inter-reader reproducibility of the measurements following a standardised protocol.

The routine assessment and monitoring of hypertension may benefit from the evaluation of arterial pulse pressure (PP) at more central locations (e.g. the aorta) rather solely at the brachial artery. Pulse Wave Ultrasound Manometry (PWUM) was previously developed by our group to provide direct, noninvasive aortic PP measurements using ultrasound elasticity imaging. Using PWUM, radial applanation tonometry, and brachial sphygmomanometry, this study investigated the feasibility of noninvasively obtaining direct PP measurements at multiple arterial locations in normotensive, pre-hypertensive, and hypertensive human subjects. Two-way ANOVA indicated a significantly higher aortic PP in the hypertensive subjects, while radial and brachial PP were not significantly different among the subject groups. No strong correlation (r < 0.45) was observed between aortic and radial/brachial PP in normal and pre-hypertensive subjects, suggesting that increases in PP throughout the arterial tree may not be uniform in relatively compliant arteries. However, there was a relatively strong positive correlation between aortic PP and both radial and brachial PP in hypertensive subjects (r = 0.68 and 0.87, respectively). PWUM provides a low-cost, non-invasive, and direct means of measuring the pulse pressure in large central arteries such as the aorta. When used in conjunction with peripheral measurement devices, PWUM allows for the routine screening of hypertension and monitoring of BP-lowering drugs based on the PP from multiple arterial sites.

This paper aims to summarize and map contemporary views on some contentious aspects of arterial hemodynamics that have remained unresolved despite years of research. These were discussed during a workshop entitled held in London on June 14 and 15, 2016. To do this we formulated a list of potential consensus statements informed by discussion at the meeting in London and quantified the degree of agreement and invited comments from the participants of the workshop. Overall the responses and comments show a high measure of quantitative agreement with the various proposed 'consensus' statements. Taken together, these statements seem a useful basis for proceeding with a more detailed and comprehensive consensus document on the current understanding and approaches to analysis of the pulse waveform. Future efforts should be directed at identifying remaining areas of dispute and future topics for research.

Maximum aerobic capacity (VOmax) is associated with lower cardiovascular and total mortality. Step tests can be used to provide an estimate of (VOmax) in epidemiological or home-based studies. We compared different methods of estimation of VO and heart rate recovery and evaluated the relationship of these estimates with cardiovascular risk factors.

Continuous wave near infrared spectroscopy (CW NIRS) provides non-invasive technology to measure relative changes in oxy- and deoxy-haemoglobin in a dynamic environment. This allows determination of local skeletal muscle O saturation, muscle oxygen consumption ([Formula: see text]) and blood flow. This article provides a brief overview of the use of CW NIRS to measure exercise-limiting factors in skeletal muscle.

In general, a terminology shared and agreed by different stakeholders is important to facilitate communication and cooperation. This holds true in the field of vascular ageing for the benefit of global cardiovascular health. The need to promote a common language and understanding across this area was recognised by VascAgeNet, a collaborative network with relevant and diverse expertise in the vascular ageing field, supported by the European Cooperation in Science and Technology. To contribute to the spread of unified terms in the vascular ageing field, a glossary was created by VascAgeNet and this paper describes the systematic process used for its development.

Medical devices are subject to strict regulatory and approval processes to enter the market and to be used by operators and patients. These are needed to guarantee the users' safety. The different activities of these processes have important implications for all involved stakeholders and for the whole lifecycle of a medical device. The aim of this work is to provide an overview of some key aspects of the new EU Medical Device Regulation and to show why researchers, innovators and clinicians should care about it. Awareness of regulatory requirements can improve the innovation process and its efficiency in terms of both social and ethical impact, but this awareness needs to be raised in the upcoming months and years. One can shortly say "yes, one needs to take care" of the new EU Medical Device Regulation. First and foremost, it is crucial for the sake of the users' safety, which is the regulation's intrinsic goal. Second, it should not just be seen as an obstacle for new innovations in the medical domain, but as a chance as it can provide new opportunities.

Magnitudes of change in endothelial function research can be articulated using effect size statistics. Effect sizes are commonly used in reference to Cohen's seminal guidelines of small ( = 0.2), medium ( = 0.5), and large ( = 0.8). Quantitative analyses of effect size distributions across various research disciplines have revealed values differing from Cohen's original recommendations. Here we examine effect size distributions in human endothelial function research, and the magnitude of small, medium, and large effects for macro and microvascular endothelial function.

In December 2019, an outbreak of pneumonia caused by a novel Coronavirus (COVID-19) spread rapidly worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, the cardiovascular system is extensively affected at multiple levels. Due to the unprecedented consequences of the COVID-19 pandemic, the ARTERY society decided to launch the Covid-19 effects on ARTErial StIffness and vascular AgeiNg (CARTESIAN) study - the first international multicentre study into the effects of COVID-19 on non-invasive biomarkers of vascular ageing. The main study objective is to evaluate the presence of Early Vascular Ageing (EVA) 6 and 12 months after COVID-19 infection. Secondary objectives are to study the effect of COVID-19 disease severity on EVA, to investigate the role of psychosocial factors in COVID-19 induced EVA, and to investigate the potential modifying effect of comorbidities and chronic treatments. In the CARTESIAN study, a broad array of cardiovascular measurements, including carotid-femoral pulse wave velocity, central blood pressure, carotid ultrasound, brachial flow-mediated dilatation, will be performed. To date, 43 centres from 21 countries have agreed to participate, with an expected study population of >2500 individuals. To our knowledge, CARTESIAN will be the first study to provide insight into the relationship between COVID-19, its severity, and early vascular ageing in a large cohort, potentially enabling future care and diagnostics to be more focused on the most vulnerable.

Arteries can stiffen via different mechanisms due to the distending effects of blood pressure, the extracellular (ECM) and vascular smooth muscle cells (VSMC). This short review discusses how these simple models can be applied to the complex biomechanics of arteries to gain physiological insight into why an individual's arteries are stiff and identify new therapeutic strategies. In the Multi-Ethnic Study of Atherosclerosis, the important question of whether arteries stiffen with aging due to load-dependent or structural stiffening was investigated. Structural stiffening was consistently observed with aging, but load-dependent stiffening was highly variable. Importantly, the high load-dependent stiffness was associated with future cardiovascular disease events, but structural stiffness was not. Clinical studies in older, hypertensive adults surprisingly show that decreasing vascular smooth muscle tone can cause clinically significant increases in arterial stiffness. To understand this paradox, the author developed a model simple enough for clinical data but with biologically relevant extracellular matrix (ECM) and vascular smooth muscle cell (VSMC) stiffness parameters. The effect of VSMC tone on arterial stiffness depends on the ECM-VSMC stiffness ratio. Future research is needed to develop a framework that incorporates both the blood pressure dependence of arterial stiffness and the VSMC-ECM interaction on hemodynamics. This could result in personalized arterial stiffness treatments and improved CVD outcomes. The subtitle of this review is "Learning to De-Stiffen Arteries" because our results have so far only shown that we can acutely make arteries stiffer. We are optimistic though that the findings and the analytic techniques covered here will be one of the many steps along the path of the arterial stiffness research community learning how to de-stiffen arteries.