title: Cardiac metabolic alterations in hypertensive obese pigs.
abstract: 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.
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Zi-Lun
authors.initials: ZL
authors.lastname: Li
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Aditya S
authors.initials: AS
authors.lastname: Pawar
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.).
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: From the Divisions of Nephrology and Hypertension (X.Z., Z.-L.L., A.E., B.E., A.S.P., X.-Y.Z., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, MN; and Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Z.-L.L.). lerman.lilach@mayo.edu.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004579:Electron Transport / Q000502:physiology; D005355:Fibrosis; D006439:Hemodynamics / Q000502:physiology; D006973:Hypertension / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009765:Obesity / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
keywords: hypertension; mitochondrial turnover; obesity; renal artery stenosis