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Salusin-? Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma.

ABSTRACT: The pathophysiological mechanisms for vascular lesions in diabetes mellitus (DM) are complex, among which endothelial dysfunction plays a vital role. Therapeutic target against endothelial injury may provide critical venues for treatment of diabetic vascular diseases. We recently identified that salusin-? contributed to high glucose-induced endothelial cell apoptosis. However, the roles of salusin-? in DM-induced endothelial dysfunction remain largely elusive. Male C57BL/6J mice were used to induce type 2 diabetes mellitus (T2DM) model. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose/high fat (HG/HF) medium. We demonstrated increased expression of salusin-? in diabetic aortic tissues and high-glucose/high-fat- (HG/HF-) incubated HUVECs. Disruption of salusin-? by shRNA abrogated the reactive oxygen species (ROS) production, inflammation, and nitrotyrosine content of HUVECs cultured in HG/HF medium. The HG/HF-mediated decrease in peroxisome proliferator-activated receptor ? (PPAR?) expression was restored by salusin-? shRNA, and PPAR? inhibitor T0070907 abolished the protective actions of salusin-? shRNA on endothelial injury in HG/HF-treated HUVECs. Salusin-? silencing obviously improved endothelium-dependent vasorelaxation, oxidative stress, inflammatory response, and nitrative stress in diabetic aorta. Taken together, our results highlighted the essential role of salusin-? in pathological endothelial dysfunction, and salusin-? may be a promising target in treatment of vascular complications of DM.

SUBMITTER: Sun HJ

PROVIDER: S-EPMC5735326 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Salusin-β Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma.

Sun Hai-Jian HJ Chen Dan D Wang Pei-Yao PY Wan Ming-Yu MY Zhang Chen-Xing CX Zhang Zhi-Xuan ZX Lin Wei W Zhang Feng F

Oxidative medicine and cellular longevity 20171119

The pathophysiological mechanisms for vascular lesions in diabetes mellitus (DM) are complex, among which endothelial dysfunction plays a vital role. Therapeutic target against endothelial injury may provide critical venues for treatment of diabetic vascular diseases. We recently identified that salusin-β contributed to high glucose-induced endothelial cell apoptosis. However, the roles of salusin-β in DM-induced endothelial dysfunction remain largely elusive. Male C57BL/6J mice we ...[more]

PMID: 29359008

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Project description:Preeclampsia is a hypertensive disorder of pregnancy associated with vascular dysfunction and cardiovascular risk to offspring. We hypothesize that endothelial PPARγ (peroxisome proliferator-activated receptor-γ) provides cardiovascular protection in offspring from pregnancies complicated by hypertension. C57BL/6J dams were bred with E-V290M sires, which express a dominant-negative allele of PPARγ selectively in the endothelium. Arginine vasopressin was infused throughout gestation. Vasopressin elevated maternal blood pressure at gestational day 14 to 15 and urinary protein at day 17 consistent. Systolic blood pressure and vasodilation responses to acetylcholine were similar in vasopressin-exposed offspring compared to offspring from control pregnancies. We treated offspring with a subpressor dose of angiotensin II to test if hypertension during pregnancy predisposes offspring to hypertension. Male and female angiotensin II-treated E-V290M offspring from vasopressin-exposed but not control pregnancy exhibited significant impairment in acetylcholine-induced relaxation in carotid artery. Endothelial dysfunction in angiotensin II-treated E-V290M vasopressin-exposed offspring was attenuated by tempol, an effect which was more prominent in male offspring. Nrf2 (nuclear factor-E2-related factor) protein levels were significantly elevated in aorta from male E-V290M offspring, but not female offspring compared to controls. Blockade of ROCK (Rho-kinase) signaling and incubation with a ROCK2-specific inhibitor improved endothelial function in both male and female E-V290M offspring from vasopressin-exposed pregnancy. Our data suggest that interference with endothelial PPARγ in offspring from vasopressin-exposed pregnancies increases the risk for endothelial dysfunction on exposure to a cardiovascular stressor in adulthood. This implies that endothelial PPARγ provides protection to cardiovascular stressors in offspring of a pregnancy complicated by hypertension and perhaps in preeclampsia.

Dataset Information

Salusin-? Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma.

Publications

Salusin-<i>β</i> Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma.

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