Calcitonin gene-related peptide inhibits angiotensin II-induced endothelial progenitor cells senescence through up-regulation of klotho expression

Zhou, Zhi; Hu, Chang-Ping; Wang, Chenjing; Li, Tingting; Peng, Jun; Li, Yuan‐Jian

doi:10.1016/j.atherosclerosis.2010.08.050

Cited by 59 publications

(37 citation statements)

References 29 publications

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“…The experiments revealed that both Klotho levels and telomere length decrease with the number of PD; the decrease in Klotho expression preceded telomere shortening, but this does not imply that Klotho causes the subsequent telomere shortening. A recent report by Liu et al (2011) shows that ectopic Klotho transfected into HUVEC extended their replicative potential and other authors have demonstrated that partial inhibition of Klotho expression resulted in a increase in endothelial progenitor cell senescence (Zhou et al, 2010) so it is likely that intracellular Klotho protein may retard cell ageing. In our aging experiments, cells were viable because the decrease in Klotho was only partial and it did not become totally absent, even at PD 42.…”

Section: Discussionmentioning

confidence: 96%

Klotho modulates the stress response in human senescent endothelial cells

Carracedo

Buendía

Merino

et al. 2012

Mechanisms of Ageing and Development

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Section: Discussionmentioning

confidence: 96%

Klotho modulates the stress response in human senescent endothelial cells

Carracedo

Buendía

Merino

et al. 2012

Mechanisms of Ageing and Development

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“…By contrast, in cat cerebral [46], pig coronary [47] and rat mesenteric vessels [48], CGRP acts directly on VSMCs. Recently, Zhou et al reported that CGRP inhibits angiotensin II-induced endothelial progenitor cell senescence by upregulating klotho expression [49]. Other investigators also showed that re-endothelialization (e.g., vascular repair) by bone marrow-derived endothelial progenitor cells is an important determinant affecting neointima formation after vascular injury [27,50,51].…”

Section: Discussionmentioning

confidence: 99%

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

Yang

Sakurai

Kamiyoshi

et al. 2013

Journal of Molecular and Cellular Cardiology

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Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after percutaneous coronary intervention. Calcitonin gene-related peptide (CGRP) is produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene.Originally identified as a strongly vasodilatory neuropeptide, CGRP is now known to be a pleiotropic peptide widely distributed in various organs and tissues. Our aim was to investigate the possibility that CGRP acts as an endogenous vasoprotective molecule.We compared the effect of CGRP deficiency on neointima formation after wire-induced vascular injury in wild-type and CGRP knockout (CGRP-/-) mice. We found that neointima formation after vascular injury was markedly enhanced in CGRP-/-mice, which also showed a higher degree of oxidative stress, as indicated by reduced expression of nitric oxide synthase, increased expression of p47phox, and elevated levels of 4HNE, as well as greater infiltration of macrophages. In addition, CGRP-deficiency led to increased vascular smooth muscle cell (VSMC) proliferation within the neointima. By contrast, bone marrow-derived cells had little or no effect on neointima formation in CGRP-/-mice. In vitro analysis showed CGRP-treatment suppressed VSMC proliferation, migration, and ERK1/2 activity. These results clearly demonstrate that endogenous CGRP suppresses the oxidative stress and VSMC proliferation induced by vascular injury. As a vasoprotective molecule, CGRP could be an important therapeutic target in cardiovascular disease.

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“…3,4 CGRP does not play a primary role in the regulation of basal blood pressure (BP) in normal individuals 5,6 but is suggested to have protective properties, in cardiovascular disease, 7,8 including attenuation of vascular smooth muscle proliferation, 9 hyperplasia, 10,11 and stimulation of endothelial cell proliferation 12 and endothelial progenitor cells. 13 Evidence indicates the importance of CGRP in aggressive models of rodent hypertension that are centered on the kidney. 14,15 By comparison, there is little evidence of detailed analysis involving the ongoing influence of endogenous CGRP on hypertensive mechanisms and vascular remodeling, especially with regard to NO and oxidative stress pathways.…”

mentioning

confidence: 99%

An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

et al. 2014

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1056α -Calcitonin gene-related peptide (αCGRP) is a potent vasodilator 1 and a hypotensive peptide. It is primarily localized to the sensory nervous system, with a perivascular innervation and considered to be the major cardiovascular form, as compared with the structurally similar βCGRP. CGRP acts via a G-protein-coupled receptor (calcitonin-like receptor) when dimerized with a single transmembrane-spanning receptor activity-modifying protein RAMP1 2 signaling via cAMP and other pathways. 3,4 CGRP does not play a primary role in the regulation of basal blood pressure (BP) in normal individuals 5,6 but is suggested to have protective properties, in cardiovascular disease, 7,8 including attenuation of vascular smooth muscle proliferation, 9 hyperplasia, 10,11 and stimulation of endothelial cell proliferation 12 and endothelial progenitor cells. 13 Evidence indicates the importance of CGRP in aggressive models of rodent hypertension that are centered on the kidney. 14,15 By comparison, there is little evidence of detailed analysis involving the ongoing influence of endogenous CGRP on hypertensive mechanisms and vascular remodeling, especially with regard to NO and oxidative stress pathways.Sensory nerve-derived CGRP release is stimulated by mechanisms that include angiotensin II (AngII) and sympathetic nerve reflexes, 3,4 baroreflex sensitivity, 16 and sensory nerve activators. 17,18 We have investigated the AngII hypertension model in wild-type (WT) and αCGRP knockout (αCGRPKO) mice that have similar resting BP. We hypothesized that αCGRP is protective against the onset and development of hypertension, and the aim was to identify mechanisms by which αCGRP is protective in this model. The novel findings show Abstract-α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels...

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Calcitonin gene-related peptide inhibits angiotensin II-induced endothelial progenitor cells senescence through up-regulation of klotho expression

Cited by 59 publications

References 29 publications

Klotho modulates the stress response in human senescent endothelial cells

Klotho modulates the stress response in human senescent endothelial cells

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

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