Nitric oxide regulates vascular adaptive mitochondrial dynamics

Miller, Matthew W.; Knaub, Leslie A.; Olivera-Fragoso, Luis F.; Keller, Amy C.; Balasubramaniam, Vivek; Watson, P.A.; Reusch, Jane E.B.

doi:10.1152/ajpheart.00987.2012

Cited by 64 publications

(63 citation statements)

References 67 publications

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“…On the contrary, the known vasorelaxants nitroglycerin and ROCK inhibitor Y27632 not only relaxed KPSS-induced aorta constriction but also inhibited KPSS-induced increase of mitochondrial fission in smooth muscle cells of rat aorta and cultured arterial smooth muscle cells. It was reported that NO inhibited mitochondrial fission 17,18 and ROCK activation induced mitochondrial fission. 19,20 Although nitroglycerin and Y27632 have different mechanisms of vasorelaxant effects, both of them inhibited mitochondrial fission.…”

Section: Discussionmentioning

confidence: 96%

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Jin

et al. 2016

Hypertension

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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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Section: Discussionmentioning

confidence: 96%

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Jin

et al. 2016

Hypertension

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“…Furthermore, it is important to note that NO is an important inducer of mitochondrial biogenesis in vascular tissues through direct activation of PGC-1␣ (30). A recent study showed that eNOS inhibition attenuated mitochondrial adaptation to an exercise intervention in the aorta (26). Therefore, it is possible that LSS-induced SIRT1 activation contributes to the preservation of EC function via activation of a SIRT1/eNOS/PGC-1␣ signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

Kim

Lee

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Park J-Y. Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells. Am J Physiol Heart Circ Physiol 309: H425-H433, 2015. First published May 29, 2015 doi:10.1152/ajpheart.00438.2014.-The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise, which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in prehypertensive individuals and that these salutary effects are, in part, mediated by shear stress-induced mitochondrial biogenesis. Circulating levels of total (CD31 ϩ /CD42a Ϫ ) and activated (CD62E ϩ ) microparticles released by endothelial cells were significantly decreased (ϳ40% for both) after a 6-mo supervised aerobic exercise training program in individuals with prehypertension. In cultured human endothelial cells, laminar shear stress reduced the release of endothelial microparticles, which was accompanied by an increase in mitochondrial biogenesis through a sirtuin 1 (SIRT1)-dependent mechanism. Resveratrol, a SIRT1 activator, treatment showed similar effects. SIRT1 knockdown using small-interfering RNA completely abolished the protective effect of shear stress. Disruption of mitochondrial integrity by either antimycin A or peroxisome proliferator-activated receptor-␥ coactivator-1␣ small-interfering RNA significantly increased the number of total, and activated, released endothelial microparticles, and shear stress restored these back to basal levels. Collectively, these data demonstrate a critical role of endothelial mitochondrial integrity in preserving endothelial homeostasis. Moreover, prolonged laminar shear stress, which is systemically elevated during aerobic exercise in the vessel wall, mitigates endothelial dysfunction by promoting mitochondrial biogenesis. shear stress; exercise; mitochondrial biogenesis; endothelial microparticle NEW & NOTEWORTHYThis study assesses effects of aerobic exercise training on the release of microparticles from endothelial cells and corroborates these findings using an in vitro experimental exercise stimulant, laminar shear stress. Furthermore, this study demonstrated that shear stress-induced mitochondrial biogenesis mediates these effects against endothelial cell activation and injury.IN ENDOTHELIAL CELLS (ECs), mitochondria occupy a relatively small compartment of cytoplasmic volume (ϳ2-6%) than other energy demanding cell-types such as cardiomyocytes (32). The endothelial mitochondria are, however, thought to play a key regulatory role in cell signaling (39), calcium handling (44), and cell survival (49). Indeed, an impaired mit...

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“…By initiating downstream cGMP/PKG signaling, NO stimulates peroxisome proliferator-activated receptor γ coactivator 1α, which in turn activates nuclear peroxisome proliferator-activated receptor-γ receptors enhancing the synthesis of mitochondrial DNA and proteins (eg, complexes I-IV of the electron transport chain), thereby contributing to the maintenance of the mitochondrial mass and its function (including regulation of the cellular production of reactive oxygen species [ROS] and energy metabolism). [62][63][64] Overall, in terms of local vasomotor control, with few exceptions (see Vasoconstrictor Effect section of this article), NO is a powerful vasodilator that prevents or reduces vasoconstrictions.…”

Section: Normal Responses To Endothelium-derived Nomentioning

confidence: 99%

Thirty Years of Saying NO

Vanhoutte

Zhao

et al. 2016

Circulation Research

328

156

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T he historical demonstration by Furchgott and Zawadzki 1 that removal of the endothelium abrogates the in vitro vasodilator effect of acetylcholine has led to the identification 30 years ago of nitric oxide (NO) as a major endogenous local regulator of vascular tone. [2][3][4][5][6][7][8][9][10] When the ability of endothelial cells to produce NO is blunted, the ensuing vascular dysfunction sets the stage for the occurrence of cardiovascular disease in general, and atherosclerosis in particular. [11][12][13][14][15] This review focuses, stepby-step, on the bioavailability (production, action, and disposition) of endothelium-derived NO as local regulator of vascular tone in health and disease. Obviously, there is much more than NO in the control of the degree of contraction of underlying vascular smooth muscle cells exerted by the endothelial cells. Indeed, they generate also prostacyclin and hyperpolarizing signals (initiating endothelium-dependent hyperpolarization [EDH] and thus relaxation) and produce vasoconstrictor mediators (endothelium-derived contracting factors and the peptide endothelin-1); those have been discussed elsewhere in detail. 15-22 Endothelial Sources of NO NO SynthaseThree NO synthase (NOS) isozymes, which are encoded by different genes, catalyze the production of NO from l-arginine: neuronal NOS (or NOS-1), cytokine-inducible NOS (iNOS or NOS-2), and endothelial NOS (eNOS or NOS-3).6,23-25 Although iNOS can be induced (by lipopolysaccharides and inflammatory cytokines) and neuronal NOS can be present in the blood vessel

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Nitric oxide regulates vascular adaptive mitochondrial dynamics

Cited by 64 publications

References 67 publications

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

Thirty Years of Saying NO

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