MitoNEET in Perivascular Adipose Tissue Prevents Arterial Stiffness in Aging Mice.
PURPOSE
Arterial stiffness is an inevitable consequence of the aging process and is considered an early stage in the development of cardiovascular diseases. The perivascular adipose tissue (PVAT) is a distinct functional integral layer of the vasculature actively involved in blood pressure regulation and atherosclerosis development via PVAT-derived paracrine/autocrine factors. However, there is little knowledge regarding the relationship between PVAT and arterial stiffness.


METHODS
Using unique mice lacking PVAT, high-fat diet-induced obesity, and in mice overexpressing brown adipocyte selective mitoNEET, we investigated the relationship between PVAT and arterial stiffness in mice.


RESULTS
We found that lack of PVAT enhanced arterial stiffness in aging mice. High-fat diet feeding of aging C57BL/6J wild-type mice significantly induced hypertrophic PVAT and enhanced arterial stiffness. Furthermore, the expression of mitoNEET, a mitochondrial membrane protein related to energy expenditure, was significantly increased by pioglitazone treatment, while reduced in the hypertrophic PVAT induced by high-fat diet. Overexpression of mitoNEET in PVAT reduced the expression of inflammatory genes and was associated with lower pulse wave velocity in aging mice.


CONCLUSIONS
These data indicate that local PVAT homeostasis especially inflammation in PVAT is associated with arterial stiffness development. Pioglitazone-induced mitoNEET in PVAT prevents PVAT inflammation and is negatively associated with arterial stiffness. These findings provide new experimental insight into the roles of pioglitazone on PVAT in arterial stiffness and indicate that PVAT might be a target to treat or prevent cardiovascular disease.
['Chang|Lin|L|0000-0002-5621-8426', 'Zhao|Xiangjie|X|', 'Garcia-Barrio|Minerva|M|', 'Zhang|Jifeng|J|', 'Eugene Chen|Y|Y|']
D002001:Adipose Tissue, Brown D050154:Adiposity D000367:Age Factors D000375:Aging D000818:Animals D002318:Cardiovascular Diseases D059305:Diet, High-Fat D004195:Disease Models, Animal D033862:Iron-Binding Proteins D008297:Male D008565:Membrane Proteins D008810:Mice, Inbred C57BL D000074085:Mice, Knockout, ApoE D009765:Obesity D047495:PPAR gamma D000077205:Pioglitazone D015398:Signal Transduction D059289:Vascular Stiffness
mitoNEET Perivascular adipose tissue Arterial stiffness Brown adipose tissue