CCCP induces vasorelaxation by a mechanism that does not involve K channel activation in smooth muscle cells of arteries.

GDF11/BMP11, a member of TGF-β superfamily, was reported to rejuvenate heart, skeletal muscle and blood vessel architecture in aged mice. However, the rejuvenative effects of GDF11 were questioned recently. Here, we investigated the effects of GDF11 on smad and non-smad signals in human umbilical vein endothelial cells (HUVECs) and the effects of GDF11 on proliferation and migration of HUVECs and primary rat aortic endothelial cells (RAECs). GDF11 factor purchased from two different companies (PeproTech and R&D Systems) was comparatively studied. Western blot was used to detect the protein expressions. The cell viability and migration were examined by using MTT and wound healing assays. Results showed that GDF11 activated both smad1/5/8 and smad2/3 signals in HUVECs. GDF11 increased protein expression of NADPH oxidase 4(NOX4) in HUVECs. GDF11 showed no significant effect on the protein level of p38, p-p38, ERK, p-ERK, Akt, p-Akt (Ser473) and p-Akt(Thr308), but increased the protein level of p-JNK and p-AMPK in HUVECs, and these increases were inhibited by antioxidant mitoTEMPO treatment. GDF11 slightly increased cell viability after short-term treatment and slightly decreased cell viability after long-term treatment. GDF11 showed no significant effect on cell proliferation and migration. These data indicated that the notion of GDF11 as a rejuvenation-related factor for endothelial cells needs to be cautious.

H ypertension is one of the most common worldwide diseases and is a major risk factor for a variety of cardiovascular and renal events, including myocardial infarction, stroke, heart failure, and end-stage renal disease. 1 The latest survey shows that hypertension accounts for 7% of global disability adjusted life years and 9.4 million deaths in 2010.2 Therefore, the molecular mechanisms underlying hypertension and the antihypertensive therapies have always been the topics in cardiovascular fields.Mitochondria are dynamic organelles and change their morphology through fission and fusion processes named as mitochondrial dynamics.3 Defects in mitochondrial dynamics are implicated in multiple cardiovascular diseases, for instance, the increased mitochondrial fission contributes to the impairment of endothelial function in diabetes mellitus and the hyperproliferation of pulmonary artery smooth muscle cells in pulmonary arterial hypertension. 4,5 More interestingly, Hong et al 6 show that mitochondrial fission is crucial for O 2 -induced ductus arteriosus constriction and closure at birth in human and rabbits. By using novel digital image processing/single particle tracking techniques, Giedt et al 7 show that mitochondria in endothelial cells continuously undergo fusion/fission, indicating that the onset of biological function related to mitochondrial dynamics should be prompt without needing the transcription and translation processes of mitochondrial dynamic-related proteins. Therefore, we speculate that interfering mitochondrial dynamics could show acute effects on the vascular function. In the present work, we investigate the effects of acute inhibition of mitochondrial fission on the constriction and relaxation of arteries and the underlying mechanisms. We find for the first time that mitochondrial fission of smooth muscle cells is involved in artery constriction, revealing a novel mechanism for vasoconstriction and providing a potential therapeutic target for hypertension. Abstract-Mitochondria

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