Ethanol promotes rat aortic vascular smooth muscle cell proliferation via increase of homocysteine and oxidized-low-density lipoprotein

Shirpoor, Alireza; Salami, Siamak; Khadem-Ansari, Mohammad Hassan; Ilkhanizadeh, Behrouz; Abdollahzadeh, Naseh

doi:10.1016/j.jjcc.2013.06.003

Cited by 16 publications

(13 citation statements)

References 47 publications

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“…The optimal safe dose for human pregnancy needs to be clinically defined. The association of alcohol during embryonic exposure with elevated HCy levels and FA prevention (Han et al, ; Serrano et al, ) has been confirmed since then by multiple studies in the alcohol literature (Shirpoor et al, ; Kharbanda et al, ; Kruman and Fowler, ; Prior et al, ). It appears that folate deficiency is associated with the observed dyslipidemia in the fetus and placenta from a binge level of alcohol exposure.…”

Section: Discussionmentioning

confidence: 89%

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

Linask

Han

2016

Birth Defects Research

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BackgroundEmbryonic acute exposure to ethanol (EtOH), lithium, and homocysteine (HCy) induces cardiac defects at the time of exposure; folic acid (FA) supplementation protects normal cardiogenesis (Han et al., 2009, 2012; Serrano et al., 2010). Our hypothesis is that EtOH exposure and FA protection relate to lipid and FA metabolism during mouse cardiogenesis and placentation.MethodsOn the morning of conception, pregnant C57BL/6J mice were placed on either of two FA‐containing diets: a 3.3 mg health maintenance diet or a high FA diet of 10.5 mg/kg. Mice were injected a binge level of EtOH, HCy, or saline on embryonic day (E) 6.75, targeting gastrulation. On E15.5, cardiac and umbilical blood flow were examined by ultrasound. Embryonic cardiac tissues were processed for gene expression of lipid and FA metabolism; the placenta and heart tissues for neutral lipid droplets, or for medium chain acyl‐dehydrogenase (MCAD) protein.ResultsEtOH exposure altered lipid‐related gene expression on E7.5 in comparison to control or FA‐supplemented groups and remained altered on E15.5 similarly to changes with HCy, signifying FA deficiency. In comparison to control tissues, the lipid‐related acyl CoA dehydrogenase medium length chain gene and its protein MCAD were altered with EtOH exposure, as were neutral lipid droplet localization in the heart and placenta.ConclusionEtOH altered gene expression associated with lipid and folate metabolism, as well as neutral lipids, in the E15.5 abnormally functioning heart and placenta. In comparison to controls, the high FA diet protected the embryo and placenta from these effects allowing normal development. Birth Defects Research (Part A) 106:749–760, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 89%

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

Linask

Han

2016

Birth Defects Research

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“…Moreover, there is often significant adventitial remodeling in response to vessel injury and adventitial myofibroblasts are believed capable of translocating to the neo-intima and differentiating to vSMC and in this way also contribute to vascular lesion formation (Scott et al 1996; Shi et al 1996). In addition to alcohol effects on lipoproteins(Wakabayashi 2015; Hao et al 2015), we and others have described potentially important effects of alcohol on vSMC growth and migration(Sayeed et al 2002) (Cullen et al 2005; Cahill and Redmond 2012; Shirpoor et al 2013), as well as on vascular endothelial cells(Morrow et al 2008) and monocytes (Cullen et al 2005; Muralidharan et al 2014). The emergence of the concept that resident vascular stem cells, in addition to de-differentiation of vSMC and myofibroblasts as mentioned above, may become activated and contribute to arterial pathology(Orlandi 2015), together with the lack of information as to whether alcohol can regulate stem cells in the adult vessel, provoked our present study.…”

Section: Discussionmentioning

confidence: 95%

Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog‐Stimulated Stem Cell Antigen‐1 Positive Progenitor Stem Cell Expansion

Fitzpatrick

Han

Liu

et al. 2017

Alcoholism Clin & Exp Res

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Background Cell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate Ethanol (EtOH) on Sonic Hedgehog (SHh) signaling in regulating possible Sca1+ progenitor stem cell involvement during pathologic arterial remodeling. Methods and Results Partial ligation or sham-operation of the left carotid artery was performed in transgenic Sca1-eGFP mice gavaged with or without ‘daily moderate’ EtOH. The EtOH group had reduced adventitial thickening and less neo-intimal formation, compared to ligated controls. There was expansion of eGFP expressing (i.e., Sca1+) cells in remodeled vessels post-ligation (14d), especially in the neo-intima. Ethanol treatment reduced the number of Sca1+ cells in ligated vessel cross-sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 (Ptch1) and Gli2, and RT-PCR of whole vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1 - eGFP mice with the SHh signaling inhibitor cyclopamine diminished hedgehog target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh-induced differentiation to vascular smooth muscle cells. Conclusions EtOH reduces SHh - responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.

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“…Recent studies have reported that the blood homocysteine level is significantly associated with calcified plaque and the severity of CAD, assessed by computed tomography angiography and the Gensini scoring system (5-7). While there is published evidence supporting the pathophysiologic mechanisms linking homocysteine to atherosclerosis, including an increase of oxidative stress and promotion of the oxidation of low-density lipoprotein (8), stimulation of vascular smooth muscle cell proliferation (9,10) and inducement of vascular inflammation and endothelial dysfunction (11), certain studies did not support the predictive effect of homocysteine on atherothrombotic cardiovascular diseases (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Adropin is associated with hyperhomocysteine and coronary atherosclerosis

Zhao

You

Chan

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Homocysteine has been recognized as a risk factor for atherosclerosis and cardiovascular diseases. Adropin is a newly-identified energy homeostasis protein with a potential protective effect against coronary artery disease (CAD). This study attempted to measure the correlation between serum homocysteine and adropin levels in patients with CAD, and to ascertain how the two hormones could affect the severity of coronary atherosclerosis. A cohort of CAD patients who had undergone coronary angiography was prospectively recruited. The serum homocysteine and adropin levels of the patients were measured and the severity of coronary atherosclerosis was quantified with the SYNTAX score. The data were analyzed with a generalized structural equation model. In total, 170 consecutive patients were recruited with a mean serum homocysteine level of 15.9±8.3 µmol/l, and 76 (44.7%) patients were identified as hyperhomocysteinemic with a serum homocysteine level >15 µmol/l. Serum homocysteine level was found to be significantly negatively correlated with serum adropin level (r=-0.169, P=0.028). Patients with hyperhomocysteinemia had lower serum adropin levels and higher SYNTAX scores than patients without hyperhomocysteinemia. Further analysis with a generalized structural equation model showed that adropin was significantly associated with hyperhomocysteinemia (adjusted odds ratio: 0.95, 95% confidence interval: 0.93 to 0.98; P=0.002), which in turn was significantly associated with the SYNTAX score (coefficient: 4.71, 95% confidence interval: 1.39 to 8.03; P=0.005). In conclusion, the serum homocysteine level was inversely correlated with the serum adropin level in patients with CAD. A low serum adropin level was associated with hyperhomocysteinemia and more severe coronary atherosclerosis, as reflected by a higher SYNTAX score.

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Ethanol promotes rat aortic vascular smooth muscle cell proliferation via increase of homocysteine and oxidized-low-density lipoprotein

Abstract: Based on these results, we conclude that ethanol apparently exerts aortic VSMC proliferation through increase in homocysteine and Ox-LDL-mediated oxidative stress, which in turn trigger proatherogenic changes in the aortic wall.

Cited by 16 publications

References 47 publications

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog‐Stimulated Stem Cell Antigen‐1 Positive Progenitor Stem Cell Expansion

Adropin is associated with hyperhomocysteine and coronary atherosclerosis

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