Dataset Information

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

ABSTRACT:

Background

Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome.

Methods

Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD).

Results

There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-? (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group.

Conclusion

Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

SUBMITTER: Saraf R

PROVIDER: S-EPMC4713205 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

Saraf Rabya R Huang Thomas T Mahmood Feroze F Owais Khurram K Bardia Amit A Khabbaz Kamal R KR Liu David D Senthilnathan Venkatachalam V Lassaletta Antonio D AD Sellke Frank F Matyal Robina R

PloS one 20160114 1

<h4>Background</h4>Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome.<h4>Methods</h4>Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high ...[more]

PMID: 26766185

Similar Datasets

Project description:Aims:The mechanisms responsible for cardiac damage in the early stages of metabolic syndrome (MetS) remain unknown. Mitochondria are intimately associated with cellular myofibrils, with the cytoskeleton functioning as a linkage coordinator, and closely associated to the calcium release sites of the sarcoplasmic reticulum (SR). We hypothesized that early MetS is characterized by mitochondria-related myocardial damage, associated with altered cytoskeletal-mitochondria-SR interaction. Methods and results:Domestic pigs were studied after 16?weeks of diet-induced MetS, MetS treated for the last 4?weeks with the mitochondrial-targeted peptide elamipretide (ELAM; 0.1?mg/kg SC q.d), or Lean controls (n?=?6/group). Cardiac remodeling and function were assessed by fast comuted tomography. Myocardial mitochondrial structure, SR-mitochondria interaction, calcium handling, cytoskeletal proteins, oxidative stress, and apoptosis were studied ex-vivo. MetS pigs developed hyperlipidemia, hypertension, and insulin resistance, yet cardiac function was preserved. MetS-induced mitochondrial disorganization, decreased (C18:2)4 cardiolipin, disrupted ATP/ADP balance, and decreased cytochrome-c oxidase (COX)-IV activity. MetS also increased mitochondrial hydrogen peroxide (H2O2) production, decreased nicotinamide adenine dinucleotide phosphate (NADPH)/NADP and GSH/GSSG, and decreased myocardial desmin and ?2 tubulin immunoreactivity, and impaired SR-mitochondrial interaction and mitochondrial calcium handling, eliciting myocardial oxidative stress and apoptosis. ELAM improved mitochondrial organization and cardiolipin species profile, restored ATP/ADP ratio and COX-IV activity, decreased H202 production, and improved generation of NADPH and GSH. ELAM also improved cytoskeletal-mitochondria-SR interaction and mitochondrial calcium handling, attenuating oxidative stress, and apoptosis. Conclusions:Disorganization of cardiomyocyte cytoskeletal-mitochondria-SR network is associated with cardiac reversible changes in early MetS, preceding overt cardiac dysfunction. These findings may introduce novel therapeutic targets for blunting cardiac damage in early MetS.

Dataset Information

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

Background

Methods

Results

Conclusion

Publications

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

Similar Datasets

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