GHSR-1a is a novel pro-angiogenic and anti-remodeling target in rats after myocardial infarction

Yuan, Mingjie; Wang, Tao; Kong, Bin; Wang, Xin; Huang, Congxin; Wang, Danny

doi:10.1016/j.ejphar.2016.06.032

Cited by 22 publications

(14 citation statements)

References 32 publications

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“…The MI model was made by ligating of the left anterior descending coronary artery as previously described. 20) In the Fisetin + MI group, rats received a daily intraperitoneal injection of fisetin (50 mg/kg, TOCRIS Bioscience, Bristol, UK) from seven days before surgery to 28 days after MI surgery. 17,19) The Sham and MI groups were administered the same volume of placebo (DMSO).…”

Section: Rat Model Of MImentioning

confidence: 99%

Fisetin Alleviates Atrial Inflammation, Remodeling, and Vulnerability to Atrial Fibrillation after Myocardial Infarction

Liu

Shen

et al. 2019

Int. Heart J.

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Atrial inflammation and fibrosis are the critical processes involved in atrial fibrillation (AF) after myocardial infarction (MI). Fisetin is a dietary flavonoid that has shown forceful anti-inflammatory and antiproliferative properties in diverse models of disease. However, fisetin's role in atrial inflammation, fibrosis, and AF vulnerability post-MI remains completely unknown. Rats were subjected to MI surgery, by left anterior descending coronary artery ligation or sham operation, and treated with DMSO or fisetin via intraperitoneal injection. After 28 days, echocardiographic parameters were performed, and AF inducibility was tested. We further evaluated the inflammation, fibrosis of left atria (LA), and related signal pathways by RT-PCR, Western blot, and staining analysis. Compared to the MI group, fisetin treatment improved cardiac function, inhibited macrophage recruitment into the LA and production of IL-1β and TNF-α, and attenuated adverse atrial fibrosis following acute myocardial infarction (AMI). Electrophysiological recordings, using an isolated perfused heart, showed that MI-induced higher inducibility of AF and prolonged AF duration, interatrial conduction time (IACT), atrial effective refractory period (AERP) were significantly alleviated by fisetin. Mechanistically, fisetin markedly increased phosphorylated AMPK (p-AMPK) levels and suppressed NF-κB p65, p38MAPK, and smad3 phosphorylation in the LA post-MI. We demonstrate that fisetin improves LA expansion, cardiac function, atrial inflammation, fibrosis, and vulnerability to AF following MI by possibly regulating AMPK/NF-κB p65 and p38MAPK/smad3 signaling pathways.

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Section: Rat Model Of MImentioning

confidence: 99%

Fisetin Alleviates Atrial Inflammation, Remodeling, and Vulnerability to Atrial Fibrillation after Myocardial Infarction

Liu

Shen

et al. 2019

Int. Heart J.

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“…Ever since its discovery in 1999 (17), ghrelin has emerged as an important therapeutic modulator of cardiac function in health and disease (18). Whereas the exact mechanisms that underpin the cardioprotective properties of ghrelin remain to be fully elucidated, various groups have shown that ghrelin prevents MI-induced sympathetic activation (6,7,19,20), inhibits myocardial apoptosis (21), promotes angiogenesis (22,23), reduces cardiac cachexia and dysfunction (24), preserves cardiac contractility (25), and attenuates cardiac remodeling (26). Although ghrelin is known to modulate coronary vasculature tone directly, at least in animal models, the few reports, to date, do not agree as to whether ghrelin dilates or constricts coronary vessels (10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels Following β-Adrenergic Receptor Blockade

et al. 2018

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Acute myocardial infarction (MI) triggers an adverse increase in cardiac sympathetic nerve activity (SNA). Whereas β-adrenergic receptor (β-AR) blockers are routinely used for the management of MI, they may also counter β-AR-mediated vasodilation of coronary vessels. We have reported that ghrelin prevents sympathetic activation following MI. Whether ghrelin modulates coronary vascular tone following MI, either through the modulation of SNA or directly as a vasoactive mediator, has never been addressed. We used synchrotron microangiography to image coronary perfusion and vessel internal diameter (ID) in anesthetized Sprague-Dawley rats, before and then again 30 minutes after induction of an MI (left coronary artery ligation). Rats were injected with either saline or ghrelin (150 µg/kg, subcutaneously), immediately following the MI or sham surgery. Coronary angiograms were also recorded following β-AR blockade (propranolol, 2 mg/kg, intravenously). Finally, wire myography was used to assess the effect of ghrelin on vascular tone in isolated human internal mammary arteries (IMAs). Acute MI enhanced coronary perfusion to nonischemicregions through dilation of small arterioles (ID 50 to 250 µm) and microvessel recruitment, irrespective of ghrelin treatment. In ghrelin-treated rats, β-AR blockade did not alter the ischemia-induced vasodilation, yet in saline-treated rats, β-AR blockade abolished the vasodilation of small arterioles. Finally, ghrelin caused a dose-dependent vasodilation of IMA rings (preconstricted with phenylephrine). In summary, this study highlights ghrelin as a promising adjunct therapy that can be used in combination with routine β-AR blockade treatment for preserving coronary blood flow and cardiac performance in patients who suffer an acute MI.

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“…By 6 months PTx, 6 all patients had normal LV function ( Table 2). Although most patients were receiving HF 7 medications, i.e., angiotensin converting enzyme (ACE) inhibitors/beta blockers/diuretics, prior to 8 transplantation, only a small number continued to receive these medications following surgery.…”

Section: Cardiac Transplant Patient Cohortmentioning

confidence: 99%

“…Images were captured with a Nikon Eclipse TE2000-S fluorescent microscope. 7 Five random fields of view were acquired for each of 4 tissue sections at 20X magnification (Nikon 8 NIS Elements v. BR 4.50.00). software.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of the Ghrelin/Growth Hormone Secretagogue Receptor System in the Human Heart Before and After Cardiac Transplantation

Sullivan

Randhawa

Stokes

et al. 2018

Preprint

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GHSR-1a is a novel pro-angiogenic and anti-remodeling target in rats after myocardial infarction

Cited by 22 publications

References 32 publications

Fisetin Alleviates Atrial Inflammation, Remodeling, and Vulnerability to Atrial Fibrillation after Myocardial Infarction

Fisetin Alleviates Atrial Inflammation, Remodeling, and Vulnerability to Atrial Fibrillation after Myocardial Infarction

Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels Following β-Adrenergic Receptor Blockade

Dynamics of the Ghrelin/Growth Hormone Secretagogue Receptor System in the Human Heart Before and After Cardiac Transplantation

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