Abstract
Cardiovascular disease (CVD) is a leading cause of hospitalization and death. CVD is characterized by impaired vasoreactivity and mitochondrial dysfunction. Perivascular adipose tissue (PVAT), considered brown adipose tissue (BAT), surrounds the vasculature and regulates its response. Preliminary data with rats housed at either their thermoneutrality (TN, 30°C) or room temperature (RT, 22°C) showed diminished vasodilation in aorta from TN rats as compared with those from RT rats (10.2% ± 4.0% (0.159 g of vasodilation capacity, starting from maximal force constriction of 1.563 g) versus 64.2% ± 5.3% (0.909 g of 1.417 g, p<0.001). TN-housed rat aorta also showed less mitochondrial respiration with lipid substrates in multiple states (p<0.05). We hypothesize that remodeling of PVAT phenotype from BAT to white adipose tissue (WAT) may alter mitochondrial lipid utilization and cause vasoreactivity dysfunction. To test this, we housed male and female rats at either RT or TN and investigated their own PVAT + aorta or PVAT from the oppositely- housed animals along with each rat’s own aorta for vasoreactivity ex situ. There was diminished vasodilation in all TN animals with PVAT + aorta (29.2% ± 3.8% (0.269 g of 0.923 g) versus 37.6% ± 6.0% (0.255 g of 0.677 g), p<0.02), with only male animals showing a significant effect from PVAT (p<0.001). In aorta of TN-housed animals analyzed with PVAT from RT-housed animals, female vessels showed an increase in vasodilation capacity as compared to controls (56.8% ± 13.6% (0.589 g of 1.037 g) versus 5.2% ± 2.3% (0.028 g of 0.534 g), p<0.001), strongly suggesting that PVAT not only regulates vasoreactivity, but can repair TN-induced diminished dilation in a sex-dependent manner. All animals at TN had significantly less mitochondrial respiration with lipid substrates (p<0.05), with no sex differences. We further observed a significantly greater amount of lipids in PVAT from male TN-housed animals as compared to that in RT-housed animals (p<0.05), consistent with a WAT phenotype. Our data support that TN alters PVAT phenotype in a sex-dependent manner, resulting in dysfunctional vasoreactivity and mitochondrial function. These targets of CVD in both male and female animals are exciting avenues for novel therapeutics.
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