Cardiac metabolic alterations in hypertensive obese pigs

Hypertension. 2015 Aug;66(2):430-6. doi: 10.1161/HYPERTENSIONAHA.115.05478. Epub 2015 Jun 15.


Obesity and hypertension are major risk factors for cardiovascular diseases, and their growing coexistence accounts for an increase in adverse cardiac events, but the mechanisms are yet to be determined. We hypothesized that obesity exacerbates mitochondrial dysregulation imposed by hypertension and augments left ventricular dysfunction. Obesity-prone Ossabaw pigs were randomized to lean (standard diet) and obese (high-fat diet), without (Lean-sham and Obese-sham) or with renovascular hypertension (Lean-hypertension and Obese-hypertension), induced after 12 weeks of diet (n=7 each). Cardiac function, myocardial perfusion and oxygenation, and microvascular remodeling were assessed 4 weeks later. Mitochondrial biogenesis signals and structural proteins, respiratory chain complex activities, and mitochondrial self-degradation were examined, as was fibrosis. Obesity alone exerted no apparent effect on mitochondrial dynamics, but aggravated in hypertensive hearts the reduction of mitochondrial proteins, deoxyribonucleic acid content, and respiratory chain complex IV subunits activity, and amplified mitochondrial self-degradation. Synergistic interaction of obesity with hypertension also exacerbated myocardial fibrosis and left ventricular diastolic dysfunction. Mitochondrial content, respiratory chain complex IV subunits activity, and mitophagy were correlated with myocardial fibrosis. These findings suggest that obesity aggravates in renovascular hypertension cardiac mitochondrial aberrations. Mitochondrial function may regulate the progression of cardiac injury and functional deterioration in hypertension concomitant with obesity.

Keywords: hypertension; mitochondrial turnover; obesity; renal artery stenosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Electron Transport / physiology
  • Fibrosis
  • Hemodynamics / physiology
  • Hypertension / complications*
  • Hypertension / etiology
  • Hypertension / metabolism
  • Mitochondria, Heart / physiology
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Obesity / complications*
  • Obesity / etiology
  • Obesity / metabolism
  • Oxidative Stress / physiology
  • Swine
  • Ventricular Dysfunction, Left / physiopathology