Single-cell transcriptomic analyses of skin vascular endothelial cells in sedentary and voluntary wheel running young mice.

Physical activity (PA) is a fundamental aspect of preventive medicine, offering profound benefits for cardiovascular health and overall well-being. Despite its widespread benefits, the molecular mechanisms underlying PA-induced improvements in microvascular functions remain poorly understood. The skin microvasculature is uniquely affected by exercise-induced shear stress, especially during thermoregulation.

Investigating the effects of a randomized, double-blinded aerobic, resistance, and cognitive training clinical trial on neurocognitive function in older adults with cardiovascular risk factors: the ACTIONcardioRisk protocol.

Background: Lifestyle factors like exercise and cognitive stimulation might help improve cognitive performance in older adults. However, studies investigating this, reported mixed results. Most of the data supporting the benefit of exercise comes from cross-sectional studies, cohort studies, or short intervention studies of 3-6 months with poorly designed control groups.

Targeting angiopoietin like-2 positive senescent cells improves cognitive impairment in adult male but not female atherosclerotic LDLr;hApoB mice.

Cellular senescence contributes to cognitive decline in brain diseases. In dyslipidemic and atherosclerotic LDLr;hApoB100 (ATX) mice-a model exhibiting vascular dysfunctions and cognitive impairment-the role of senescence was investigated by targeting angiopoietin-like 2 (angptl2), a senescence marker. Adult ATX mice of both sexes received AAV1-sh-angptl2; cognition was assessed via the Morris Water Maze, cerebrovascular functions were evaluated in vitro and in vivo and hippocampal transcriptomic signatures were analyzed using single-nuclei RNA-sequencing.

Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients.

Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary outcomes were reduced inflammation and improved endothelial function ex vivo.

Sexually dimorphic effects of angiopoietin-like 2 on energy metabolism and hypothalamic neuropeptide regulation.

Background: Adipokines regulate body weight and metabolism by targeting the hypothalamus, influencing feeding, energy expenditure (EE) and insulin sensitivity. Angiopoietin-like 2 (Angptl2) is a pro-inflammatory adipokine linking obesity to insulin resistance. Both Angptl2 and its receptor are expressed in the central nervous system.

The senolytic ABT-263 improves cognitive functions in middle-aged male, but not female, atherosclerotic LDLr;hApoB mice.

Accumulation of cerebral senescent cells may compromise the continuum between vascular and neuronal function, leading to damage and cognitive decline. Elimination of senescent cells might therefore preserve vascular and neuronal functions. To test this hypothesis, we used male and female atherosclerotic LDLr;hApoB mice (ATX-mice), a model of vascular cognitive impairment (VCI), treated with the senolytic ABT-263 for 3 months (3- to 6-month or 9- to 12-month old).

Senescence and Inflamm-Aging Are Associated With Endothelial Dysfunction in Men But Not Women With Atherosclerosis.

Coronary artery disease (CAD) is more prevalent in men than in women, with endothelial dysfunction, prodromal to CAD, developing a decade earlier in middle-aged men. We investigated the molecular basis of this dimorphism ex vivo in arterial segments discarded during surgery of CAD patients. The results reveal a lower endothelial relaxant sensitivity in men, and a senescence-associated inflammaging transcriptomic signature in endothelial cells.

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o).

Knockdown of ANGPTL2 promotes left ventricular systolic dysfunction by upregulation of NOX4 in mice.

Angiopoietin-like 2 (ANGPTL2) is a pro-inflammatory and pro-oxidant circulating protein that predicts and promotes chronic inflammatory diseases such as atherosclerosis in humans. Transgenic murine models demonstrated the deleterious role of ANGPTL2 in vascular diseases, while deletion of ANGPTL2 was protective. The nature of its role in cardiac tissues is, however, less clear.

The role of cellular senescence in profibrillatory atrial remodelling associated with cardiac pathology.

Aims: Cellular senescence is a stress-related or aging response believed to contribute to many cardiac conditions; however, its role in atrial fibrillation (AF) is unknown. Age is the single most important determinant of the risk of AF. The present study was designed to (i) evaluate AF susceptibility and senescence marker expression in rat models of aging and myocardial infarction (MI), (ii) study the effect of reducing senescent-cell burden with senolytic therapy on the atrial substrate in MI rats, and (iii) assess senescence markers in human atrial tissue as a function of age and the presence of AF.

NTPDase1/CD39 Ectonucleotidase Is Necessary for Normal Arterial Diameter Adaptation to Flow.

NTPDase1/CD39, the major vascular ectonucleotidase, exerts thrombo-immunoregulatory function by controlling endothelial P2 receptor activation. Despite the well-described release of ATP from endothelial cells, few data are available regarding the potential role of CD39 as a regulator of arterial diameter. We thus investigated the contribution of CD39 in short-term diameter adaptation and long-term arterial remodeling in response to flow using male mice.

Angiopoietin-Like Proteins: Cardiovascular Biology and Therapeutic Targeting for the Prevention of Cardiovascular Diseases.

Despite the best pharmacologic tools available, cardiovascular diseases (CVDs) remain a major cause of morbidity and mortality in developed countries. After 2 decades of research, new therapeutic targets, such as angiopoietin-like proteins (ANGPTLs), are emerging. ANGPTLs belong to a family of 8 members, from ANGPTL1 to ANGPTL8; they have structural homology with angiopoietins and are secreted in the circulation.

Increased serum S100A12 levels are associated with higher risk of acute heart failure in patients with type 2 diabetes.

Aims: The hyperglycaemic stress induces the release of inflammatory proteins such as S100A12, one of the endogenous ligands of the receptors for advanced glycation end products (RAGE). Chronic activation of RAGE has multiple deleterious effects in target tissues such as the heart and the vessels by promoting oxidative stress, inflammation by the release of cytokines, macrophages infiltration, and vascular cell migration and proliferation, causing ultimately endothelial cell and cardiomyocyte dysfunction. The aim of our study was to investigate the prognostic value of circulating S100A12 beyond established cardiovascular risk factors (CVRF) for heart failure (HF) and major adverse cardiovascular events (MACE) in a cohort of patients with type 2 diabetes.

Angiopoietin-like 2 is essential to aortic valve development in mice.

Aortic valve (AoV) abnormalities during embryogenesis are a major risk for the development of aortic valve stenosis (AVS) and cardiac events later in life. Here, we identify an unexpected role for Angiopoietin-like 2 (ANGPTL2), a pro-inflammatory protein secreted by senescent cells, in valvulogenesis. At late embryonic stage, mice knocked-down for Angptl2 (Angptl2-KD) exhibit a premature thickening of AoV leaflets associated with a dysregulation of the fine balance between cell apoptosis, senescence and proliferation during AoV remodeling and a decrease in the crucial Notch signalling.

Differences in cognitive function, cardiorespiratory fitness and BDNF concentration in physically active CHD patients vs healthy controls.

Background: Coronary heart disease (CHD) is frequently associated with cognitive impairment (CI), whereas physical exercise may improve cognition. To date, the cognitive profile of physically active CHD patients remains poorly understood. Physical activity and cognition has been associated with neurotrophic biomarkers that are positively modulated by a higher cardiorespiratory fitness (V̇ Opeak) and/or active lifestyle.

Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in atheroprotection.

Aims: The adenylate cyclase type 9 (ADCY9) gene appears to determine atherosclerotic outcomes in patients treated with dalcetrapib. In mice, we recently demonstrated that Adcy9 inactivation potentiates endothelial function and inhibits atherogenesis. The objective of this study was to characterize the contribution of ADCY9 to the regulation of endothelial signalling pathways involved in atherosclerosis.

Angptl2 is a Marker of Cellular Senescence: The Physiological and Pathophysiological Impact of Angptl2-Related Senescence.

Cellular senescence is a cell fate primarily induced by DNA damage, characterized by irreversible growth arrest in an attempt to stop the damage. Senescence is a cellular response to a stressor and is observed with aging, but also during wound healing and in embryogenic developmental processes. Senescent cells are metabolically active and secrete a multitude of molecules gathered in the senescence-associated secretory phenotype (SASP).

Design of a Randomized Placebo-Controlled Trial to Evaluate the Anti-inflammatory and Senolytic Effects of Quercetin in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Following an acute coronary syndrome, patients display an elevated inflammatory profile, promoted in part by cellular senescence. For patients requiring a coronary artery bypass (CABG) surgery, exposure to the surgical intervention and cardiopulmonary bypass further exacerbate their residual inflammation. Experimental evidence identified quercetin, a natural senolytic drug, as a cardioprotective agent against inflammatory injuries.

The role of cellular senescence in cardiac disease: basic biology and clinical relevance.

Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing and ageing. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue biology. Clinical evidence and experimental studies link cellular senescence, senescent cell accumulation, and the production and release of SASP components with age-related cardiac pathologies such as heart failure, myocardial ischaemia and infarction, and cancer chemotherapy-related cardiotoxicity.

Therapeutic Potential of Quercetin to Alleviate Endothelial Dysfunction in Age-Related Cardiovascular Diseases.

The vascular endothelium occupies a catalog of functions that contribute to the homeostasis of the cardiovascular system. It is a physically active barrier between circulating blood and tissue, a regulator of the vascular tone, a biochemical processor and a modulator of coagulation, inflammation, and immunity. Given these essential roles, it comes to no surprise that endothelial dysfunction is prodromal to chronic age-related diseases of the heart and arteries, globally termed cardiovascular diseases (CVD).

Pathological Continuum From the Rise in Pulse Pressure to Impaired Neurovascular Coupling and Cognitive Decline.

The "biomechanical hypothesis" stipulates that with aging, the cumulative mechanical damages to the cerebral microvasculature, magnified by risk factors for vascular diseases, contribute to a breach in cerebral homeostasis producing neuronal losses. In other words, vascular dysfunction affects brain structure and function, and leads to cognitive failure. This is gathered under the term Vascular Cognitive Impairment and Dementia (VCID).

Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort.

Aims/hypothesis: Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up.