Abstract
Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks (“middle-aged”) were compared to tissue or cells from mice aged 16 weeks (“adult”). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NFκB-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat.
Highlights
The importance of age as a cardiovascular risk factor is well established: epidemiological and clinical studies have shown that age is associated with increased cardiovascular mortality and risk of coronary heart disease, stroke, and death after myocardial infarction [1]
perivascular adipose tissue (PVAT) could not be weighed, but morphometric analysis revealed a significantly increased mean single adipocyte area in middle-aged mice (Supplemental Figure S1A), and similar findings were observed in Visceral (perigonadal) adipose tissue (VAT) (Supplemental Figure S1B) and brown (interscapular) adipose tissue (BAT) (Supplemental Figure S1C)
Studies in humans and animal models have examined the effects of age on vessel walls and found it to be associated with distinct phenotypical changes
Summary
The importance of age as a cardiovascular risk factor is well established: epidemiological and clinical studies have shown that age is associated with increased cardiovascular mortality and risk of coronary heart disease, stroke, and death after myocardial infarction [1]. Age increases the risk of developing restenosis, an important complication of intravascular revascularization procedures [2]. Preclinical studies on the effects of age on the vascular response to injury have yielded inconsistent results: an increased neointima formation was reported in older rats [6,7] and mice [8], whereas injury was found to induce intimal thickening in young but not in older animals [9]. Age-associated alterations of SMCs resulting in increased proliferative and migratory capacity [6] and an enhanced response to growth factor stimulation [8] may play a role
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
