Perivascular adipose tissue‐derived stromal cells contribute to vascular remodeling during aging

Abstract

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.

The effect of on-site CT-derived fractional flow reserve on the management of decision making for patients with stable chest pain (TARGET trial): objective, rationale, and design

“…Diagnostic performance of DeepFFR technique has been confirmed as previously described [10]. By learning corresponding invasive FFR values of coronary lesions from a large number of existing databases, this AI-based technology could generate neural network model by deep learning algorithm.…”

“…When subjects are randomized to the CCTA/CT-FFR arm, on-site FFR based on the CCTA imaging (DeepFFR V1.0.0, Beijing CuraCloud Technology Co., Ltd., Beijing, China) will be measured. DeepFFR workstation is very dedicated software utilizing the original CCTA imaging to meter simulated FFR values in artificial intelligence (AI) model, which has been introduced in previous article [10]. The calculation process could be summarized as follows: the first step is to extract a 3D coronary artery model and generate coronary centerlines which are similar to the routine reconstruction of CCTA.…”

Recent Developments in Vascular Adventitial Pathobiology

“…Nevertheless, it has since been discovered that PVAT regulates vascular tone, both through contractile and anticontractile regulation, vessel pathobiology in inflammation, angiogenesis, neointimal formation, and vascular fibrosis. 81 PVAT dysfunction is promoted by vascular injury, aging, obesity, and metabolic syndrome, and may impact adventitial remodeling during the early stages of vascular injury. 82 Communication between cells in the PVAT and cells residing in the other layers of the blood vessel wall occurs through the VV or through paracrine signaling.…”

Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications

“…The differentiation capacities of PVAT-derived stromal cells (PVASCs) are altered during aging. Also, the deletion of PGC-1α (proliferator-activated receptor-gamma and coactivator 1 alpha) in aged PVASCs exacerbates arterial remodeling and attenuates the browning of adipose tissue [82]. A recent study has revealed that the mineralocorticoid receptor (MR) is activated in the mitochondria of PVAT in obese mice, which causes premature-aging in adipose tissue and senescence, resulting in the loss of the anticontractile effects [83].…”