Loss of Perivascular Adipose Tissue upon PPARγ Deletion in Smooth Muscle Cells Impairs Intravascular Thermoregulation and Enhances Atherosclerosis
Background—Perivascular adipose tissue (PVAT) surrounds most vessels and shares common features with brown adipose tissue (BAT). Whereas adaptive thermogenesis in BAT increases energy expenditure and is beneficial for metabolic diseases, little is known on 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 demonstrate 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 with cellular metabolic processes. In a mouse model deficient in PPARγ in smooth muscle cells (SMPG KO mice), we uncovered a complete absence of PVAT surrounding the vasculature likely due to PPARγ deletion also in the perivascular adipocyte precursor cells. Lack of PVAT, resulting in loss of its thermogenic activity, impairs vascular homeostasis causing temperature loss and endothelial dysfunction. We further show 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. Pro-inflammatory cytokine expression in PVAT is not altered upon cold exposure. 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 upon cold acclimation. This thermogenic capacity of PVAT plays an important protective role in the pathogenesis of atherosclerosis.
- brown adipose tissue
- cold exposure
- intravascular thermoregulation
- perivascular adipose tissue
- Received March 7, 2012.
- Accepted June 6, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited