generation-characterization-right-ventricular-myocardial-infarction

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...

Southern Medical University

Investigate the effect and mechanism of metformin on the development of metabolic syndrome related atherosclerosis.Transfecting EGFP-CLIP170 or EGFP-Pdlim5 plasmid to the mouse aortic smooth muscle cell line, to test the expression of p-AMPK, pCLIP-170 and pPdlim5, and observe the microtubule or the actin skeleton system by immunofluorescence staining. Scratch the cells to perform wound healing experiment, stimulating the cells with gradient metformin (0, 0.5, 1 mmol/L) for 8 h, and observe the change of the scratch size and the dynamic change of cell skeleton and migration . ApoE mice were injected with streptozotocin and followed by 8 weeks of high fat diet to induce metabolic syndrome model. In the therapeutic group, mice were treated metformin (Met) instead of saline in control group (Control, CTL group). In the end, the whole aorta and its root were isolated and performed oil red O staining and immol/Lunostaining of α-SMA to evaluate the migration of smooth muscle cells and the accumulation of lipids in the aorta.Mouse aortic smooth muscle cells showed an enhanced stress fiber and focal adhesion which representing the dynamic change of actin skeleton after Met stimulation, while the tubulin system rarely showed any change to Met. In animal model, The staining of α-SMA showed smooth muscle cells migrated to the intima or even to the lipid area from the media of aorta in CTL group compared to the Met group. Oil red O staining showed a reduced accumulation of lipids in the Met group than the controls ( < 0.05).Metformin reduces the formation of atherosclerosis by inhibiting the migration of smooth muscle cells through modulating cellular actin skeleton system in mice.

[Metformin inhibits aortic atherosclerosis in mice by regulating actin skeleton in vascular smooth muscle cells].

 Our previous work revealed that AMP-activated protein kinase (AMPK) activation inhibits vascular smooth muscle cell migration  by phosphorylating PDZ and LIM domain 5 (Pdlim5). As metformin is an AMPK activator, we used a mouse vascular smooth muscle cell (VSMC) line and a  mice to investigate whether metformin could inhibit the migration of VSMCs  and in a wire-injury model . It is recognized that VSMCs contribute to the major composition of atherosclerotic plaques. In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, we utilized ApoE male mice to investigate whether metformin could suppress diabetes-accelerated atherosclerosis by inhibition of VSMC migration  the AMPK-Pdlim5 pathway.  The mouse VSMC cell line was exogenously transfected wild type, phosphomimetic, or unphosphorylatable Pdlim5 mutant before metformin exposure.  mice were treated with saline solution or metformin after these were subjected to wire injury in the carotid artery to study whether metformin could inhibit the migration of medial VSMCs into the neo-intima. In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, ApoE male mice were divided randomly into control, streptozocin (STZ), and high-fat diet (HFD)-induced diabetes mellitus; STZ+HFD together with metformin or Pdlim5 mutant carried the adenovirus treatment groups.  It was found that metformin could induce the phosphorylation of Pdlim5 and inhibit cell migration as a result. The exogenous expression of phosphomimetic S177D-Pdlim5 inhibits lamellipodia formation and migration in VSMCs. It was also demonstrated that VSMCs contribute to the major composition of injury-induced neointimal lesions, while metformin could alleviate the occlusion of the carotid artery. The data of ApoE mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin.  The activation of the AMPK-Pdlim5 pathway by metformin could interrupt the migratory machine of VSMCs and inhibit cell migration  and . The maintenance of AMPK activity by metformin is beneficial for suppressing diabetes-accelerated atherosclerosis.

Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK-Pdlim5 Pathway.

Response by He et al to Letter Regarding Article, "Antihypertrophic Memory After Regression of Exercise-Induced Physiological Myocardial Hypertrophy Is Mediated by the Long Noncoding RNA Mhrt779".

Article	Year
[Metformin inhibits aortic atherosclerosis in mice by regulating actin skeleton in vascular smooth muscle cells]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University\| PubMed ID: 31852643	2019
Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK-Pdlim5 Pathway. Frontiers in cardiovascular medicine\| PubMed ID: 34368251	2021
Response by He et al to Letter Regarding Article, "Antihypertrophic Memory After Regression of Exercise-Induced Physiological Myocardial Hypertrophy Is Mediated by the Long Noncoding RNA Mhr... Circulation\| PubMed ID: 34662156	2021

Mingyuan He

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