Loss of perivascular adipose tissue due to PPAR-γ deletion impaired intravascular thermoregulation and exacerbated atherosclerosis by preventing cold-induced lipid clearance and endothelial protection.
Does cold exposure prevent atherosclerosis and improve endothelial function in mice with intact perivascular adipose tissue?
Perivascular adipose tissue possesses thermogenic properties similar to brown adipose tissue that protect against endothelial dysfunction and atherosclerosis during cold acclimation.
BACKGROUND: Perivascular adipose tissue (PVAT) surrounds most vessels and shares common features with brown adipose tissue (BAT). Although adaptive thermogenesis in BAT increases energy expenditure and is beneficial for metabolic diseases, little is known about the role of PVAT in vascular diseases such as atherosclerosis. We hypothesize that the thermogenic function of PVAT regulates intravascular temperature and reduces atherosclerosis. METHODS AND RESULTS: PVAT shares similar structural and proteomics with BAT. We demonstrated that PVAT has thermogenic properties similar to BAT in response to cold stimuli in vivo. Proteomics analysis of the PVAT from mice housed in a cold environment identified differential expression in proteins highly related to cellular metabolic processes. In a mouse model deficient in peroxisome proliferator-activated receptor-γ in smooth muscle cells (SMPG KO mice), we uncovered a complete absence of PVAT surrounding the vasculature, likely caused by peroxisome proliferator-activated receptor-γ deletion in the perivascular adipocyte precursor cells as well. Lack of PVAT, which results in loss of its thermogenic activity, impaired vascular homeostasis, which caused temperature loss and endothelial dysfunction. We further showed that cold exposure inhibits atherosclerosis and improves endothelial function in mice with intact PVAT but not in SMPG KO mice as a result of impaired lipid clearance. Proinflammatory cytokine expression in PVAT is not altered on exposure to cold. Finally, prostacyclin released from PVAT contributes to the vascular protection against endothelial dysfunction. CONCLUSIONS: PVAT is a vasoactive organ with functional characteristics similar to BAT and is essential for intravascular thermoregulation of cold acclimation. This thermogenic capacity of PVAT plays an important protective role in the pathogenesis of atherosclerosis.
Chang et al. (Thu,) conducted a other in Atherosclerosis. Peroxisome proliferator-activated receptor-γ deletion in smooth muscle cells (SMPG KO) and cold exposure vs. Mice with intact PVAT was evaluated on Atherosclerosis and endothelial function. Loss of perivascular adipose tissue due to PPAR-γ deletion impaired intravascular thermoregulation and exacerbated atherosclerosis by preventing cold-induced lipid clearance and endothelial protection.