Defective macroautophagy/autophagy and mitochondrial dysfunction are known to stimulate senescence. The regulator PPARGC1A (peroxisome proliferator activated receptor gamma, coactivator 1 alpha) regulates biogenesis, reducing senescence of vascular smooth muscle cells (VSMCs); however, it is unknown whether autophagy mediates PPARGC1A-protective effects on Using

With the increasing appreciation for sex as a biological variable and inclusion of female mice in research, it is important to understand influence estrous cycle on physiological function. Sex hormones are known modulate vascular function, but effects mouse phase arterial stiffness, endothelial estrogen receptor expression remain unknown. In 23 C57BL/6 (6 mo age), we determined stage via vaginal cytology plasma hormone concentrations. Aortic assessed by pulse wave velocity, was lower during...

Vascular aging is characterized by a tandem increase in pulse pressure and large elastic artery stiffness. Greater stiffness of the arteries leads to elevated transmitted into cerebral circulation, causing dysfunction. However, little known females about age-related stiffening impacts high on vasculature. To examine effects sex age response pressure, we studied collected from young old female male C57BL/6 mice. Isolated were exposed ex vivo static low pressure. Exposure impaired...

Adiponectin (adipoq), the most abundant hormone in circulation, has many beneficial effects on cardiovascular system, part by preserving contractile phenotype of vascular smooth muscle cells (VSMCs). However, lack adiponectin or its receptor and treatment with recombinant have shown contradictory plaque mice. RNA sequence Adipoq+/+ adipoq-/- VSMCs from male aortas identified a critical role for AKT signaling, extracellular matrix (ECM), TGF-β signaling. Upregulation activity mediated...

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents stiffening advancing age, but the effects of pyridoxamine on cerebral vasculature or cognition is unknown. The purpose this study was to investigate blood pressure, stiffness, function, function old mice. Old male C57BL/6 mice consumed either (2 g/L) vehicle control drinking water for ∼7.5 months were compared young From pre-...

Abstract Introduction Cigarette smoke (CS) invokes an inflammatory response associated with vascular dysfunction and atherosclerosis. The role of sex nicotine in CS effects on cardiovascular function atherosclerosis is unexplored. Aims Methods Male female C57Bl/6 WT (wild type) ApoE-/- mice were exposed to access chow water ad libitum for 16 weeks fill this gap. Heart rate endothelial measured the aorta mice, while lipid profile, cytokines, chemokines, plaque area composition assessed mice....

Smoking is the foremost modifiable risk factor for cardiovascular disease, leading cause of death in U.S., yet almost 14% American adults continue to smoke. Cigarettes contain nicotine, a highly addictive stimulant which prevents users from quitting smoking without withdrawal. Nicotine and other chemicals cigarette smoke damage endothelium, process that turn influences smooth muscle cells contributes atherosclerosis or plaque build-up arteries causing diseases. Gender differences have...

Abstract Adiponectin, a hormone highly abundant in circulation, has many beneficial effects atherosclerosis; however, gene deficiency of this or its receptor have shown detrimental on plaque burden mice. Our objective was to understand the role sex and aging adiponectin content, inflammation, mechanisms regulating phenotype adipoq -/- vascular smooth muscle cells (VSMCs). Even 50% reduction expression led males an increase females, compared with apoe controls. Plaque may be attributable...

The hormone adiponectin has many beneficial effects in atherosclerosis, as gene deficiency or its receptor shown detrimental on plaque burden mice. Our objective was to understand the potential roles aortic content, inflammation, and markers of cardiovascular disease according sex age. To study influence status we used young male female adipoq−/−apoe−/−, adipoq+/−apoe−/−, apoe−/− mice, which were given a high-fat diet (HFD). Even 50% reduction expression led males an increase females...

As females age, they transition through menopause, experiencing a decrease in estrogen and an increase cardiovascular neurodegenerative disease risk. Most standard rodent chows contain phytoestrogen-rich soybean meal, which can mimic the effects of estrogen. Understanding impact this meal on vascular outcomes is crucial to proper experimental design. Thus, study aimed compare soy-free cerebral artery endothelial function cognitive ovariectomized mice. Young female C57Bl/6J mice (

Abstract cigarette smoke (CS) invokes an inflammatory response involving increased levels of circulating cytokines and chemokines, vascular dysfunction, atherosclerosis. The role sex nicotine in CS effects cardiovascular function atherosclerosis is unexplored. To assess the sex, male female C57Bl/6 WT (wild type) ApoE -/- mice were exposed to for 16 weeks bridge this literature gap. Heart rate endothelial measured aorta mice, while plasma lipids, chemokines aortic plaque burden was assessed...

Abstract Declines in vascular integrity are potential contributors to Alzheimer’s disease (AD) as these result increased blood-brain barrier permeability and, a consequence, accelerate neuroinflammation and cognitive impairment. Roundabout guidance receptor 4 (Robo4) is primarily expressed endothelial cells stabilizes the vasculature, thus, has protect brain AD. To study effect of Robo4 on function context AD, we compared knockout wildtype mice crossed with without AD mutations (APP/tau). We...

Two of the greatest risk factors for late-onset Alzheimer’s disease (LOAD) are age and APOE4 genotype. The gene encoding apolipoprotein E ( APOE) has three isoforms in humans E2, E3, E4). E3 highest prevalence, while E4 exponentially increases AD. Additionally, it is well known that genotype accompanied by an altered cerebral blood flow. However, mechanisms underlying these flow changes individuals remain unclear may be mediated to artery structure function. We aimed determine if APOE alters...

Abstract Background Stiffening of the large arteries is a hallmark feature vascular aging and associated with cognitive impairment Alzheimer’s disease pathology. Increased artery stiffness leads to higher‐than‐normal pulse pressure in cerebral circulation, damaging endothelial cells. It known that short‐term exposure stiffer causes dysfunction hypoperfusion young mice. However, impact long‐term on cerebrovascular function unknown. As there are sex differences risk, we sought understand...

Vascular smooth muscle cells (VSMCs) play an essential role in the development and progression of atherosclerosis. The phenotypic switch from contractile to synthetic induces excess proliferation migration VSMCs into intima contributing plaque formation. Adiponectin (Adpn) is adipokine that regulates glucose metabolism through AMPK plays beneficial roles We hypothesize Adpn promotes phenotype VSMC reducing VSMCs, a process protective against Differentiation, proliferation, signaling...

Females and individuals with greater large artery stiffness are at higher risk for developing cognitive impairment. Lower cerebral perfusion vasoreactivity associated impairment, but it is unknown if sex arterial interact to affect these. We hypothesized that chronic exposure stiffer arteries, modeled by elastin haploinsufficiency, would cause impaired in middle-aged mice. studied male female (15 months, n=18, 17) wildtype (Eln +/+ ) haploinsufficient +/- mice (n=20,15). Cerebral was...

The major risk factors for late-onset Alzheimer’s Disease (LOAD) include old age, female sex and the APOE4 allele. Post-menopausal females with an allele have higher rates of LOAD compared age-matched males allele, suggesting interaction between APOE genotype estrogen deficiency. Importantly, cerebrovascular dysfunction is a contributor to risk. However, it unknown if deficiency interact impact function.Young homozygous APOE3 mice (n=4-6 per group; ~6 months old) fed high-fat,...

We hypothesize that nicotine plays a role in the progression of atherosclerosis by inducing VSMC phenotypic switching and cell migration from media to an inner layer–the intima. This forms new layer called neointima, which becomes plaque with lipid-rich necrotic core fibrous cap. The cap confers protection against rupture stroke or heart attack. However, VSMCs can contribute thinning secreting metalloproteinases (MMPs) degrade extracellular matrix (ECM) creating prone rupture. Our lab will...