Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia

Antonio D. Lassaletta, Louis M. Chu, Michael P. Robich, Nassrene Y. Elmadhun, Jun Feng, Thomas A. Burgess, Roger J. Laham, Michael Sturek, Frank W. Sellke

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functional measurements followed by cardiac harvest. Both OHC and OHCM animals developed significantly greater weight gain, total cholesterol, and LDL:HDL ratio compared to OC controls. Metforminadministration reversed diet-induced hypertension and glucose intolerance. There were no differences in global and regional contractility, myocardial perfusion, capillary and arteriolar density, or total protein oxidation between groups. Myocardial protein expression of VEGF, PPAR-α, c, and d was significantly increased in the OHC and OHCM groups. Microvessel reactivity was improved in the OHC and OHCM groups compared to controls, and correlated with increased p-eNOS expression. Overfed Ossabaw miniswine develop several components of metabolic syndrome. However, impairments of myocardial function, neovascularization and perfusion were not present, and microvessel reactivity was paradoxically improved in hypercholesterolemic animals. The observed cardioprotection despite metabolic derangements may be due to lipid-dependant upregulation of the PPAR pathway which is anti-inflammatory and governs myocardial fatty acid metabolism.

Original languageEnglish
Article number0243
JournalBasic Research in Cardiology
Volume107
Issue number2
DOIs
StatePublished - 2012

Fingerprint

Swine
Ischemia
High Fat Diet
Peroxisome Proliferator-Activated Receptors
Metformin
Cholesterol
Microvessels
Perfusion
Diet
Lipids
Glucose Intolerance
LDL Cholesterol
HDL Cholesterol
Vascular Endothelial Growth Factor A
Weight Gain
Coronary Vessels
Proteins
Anti-Inflammatory Agents
Up-Regulation
Fatty Acids

Keywords

  • Cardioprotection
  • Chronic ischemia
  • Metabolic syndrome
  • Ossabaw

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Lassaletta, A. D., Chu, L. M., Robich, M. P., Elmadhun, N. Y., Feng, J., Burgess, T. A., ... Sellke, F. W. (2012). Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia. Basic Research in Cardiology, 107(2), [0243]. https://doi.org/10.1007/s00395-012-0243-y

Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia. / Lassaletta, Antonio D.; Chu, Louis M.; Robich, Michael P.; Elmadhun, Nassrene Y.; Feng, Jun; Burgess, Thomas A.; Laham, Roger J.; Sturek, Michael; Sellke, Frank W.

In: Basic Research in Cardiology, Vol. 107, No. 2, 0243, 2012.

Research output: Contribution to journalArticle

Lassaletta, Antonio D. ; Chu, Louis M. ; Robich, Michael P. ; Elmadhun, Nassrene Y. ; Feng, Jun ; Burgess, Thomas A. ; Laham, Roger J. ; Sturek, Michael ; Sellke, Frank W. / Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia. In: Basic Research in Cardiology. 2012 ; Vol. 107, No. 2.
@article{fa6902edc7524b98aa45d24cd7ae87d9,
title = "Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia",
abstract = "Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functional measurements followed by cardiac harvest. Both OHC and OHCM animals developed significantly greater weight gain, total cholesterol, and LDL:HDL ratio compared to OC controls. Metforminadministration reversed diet-induced hypertension and glucose intolerance. There were no differences in global and regional contractility, myocardial perfusion, capillary and arteriolar density, or total protein oxidation between groups. Myocardial protein expression of VEGF, PPAR-α, c, and d was significantly increased in the OHC and OHCM groups. Microvessel reactivity was improved in the OHC and OHCM groups compared to controls, and correlated with increased p-eNOS expression. Overfed Ossabaw miniswine develop several components of metabolic syndrome. However, impairments of myocardial function, neovascularization and perfusion were not present, and microvessel reactivity was paradoxically improved in hypercholesterolemic animals. The observed cardioprotection despite metabolic derangements may be due to lipid-dependant upregulation of the PPAR pathway which is anti-inflammatory and governs myocardial fatty acid metabolism.",
keywords = "Cardioprotection, Chronic ischemia, Metabolic syndrome, Ossabaw",
author = "Lassaletta, {Antonio D.} and Chu, {Louis M.} and Robich, {Michael P.} and Elmadhun, {Nassrene Y.} and Jun Feng and Burgess, {Thomas A.} and Laham, {Roger J.} and Michael Sturek and Sellke, {Frank W.}",
year = "2012",
doi = "10.1007/s00395-012-0243-y",
language = "English",
volume = "107",
journal = "Basic Research in Cardiology",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "2",

}

TY - JOUR

T1 - Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia

AU - Lassaletta, Antonio D.

AU - Chu, Louis M.

AU - Robich, Michael P.

AU - Elmadhun, Nassrene Y.

AU - Feng, Jun

AU - Burgess, Thomas A.

AU - Laham, Roger J.

AU - Sturek, Michael

AU - Sellke, Frank W.

PY - 2012

Y1 - 2012

N2 - Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functional measurements followed by cardiac harvest. Both OHC and OHCM animals developed significantly greater weight gain, total cholesterol, and LDL:HDL ratio compared to OC controls. Metforminadministration reversed diet-induced hypertension and glucose intolerance. There were no differences in global and regional contractility, myocardial perfusion, capillary and arteriolar density, or total protein oxidation between groups. Myocardial protein expression of VEGF, PPAR-α, c, and d was significantly increased in the OHC and OHCM groups. Microvessel reactivity was improved in the OHC and OHCM groups compared to controls, and correlated with increased p-eNOS expression. Overfed Ossabaw miniswine develop several components of metabolic syndrome. However, impairments of myocardial function, neovascularization and perfusion were not present, and microvessel reactivity was paradoxically improved in hypercholesterolemic animals. The observed cardioprotection despite metabolic derangements may be due to lipid-dependant upregulation of the PPAR pathway which is anti-inflammatory and governs myocardial fatty acid metabolism.

AB - Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functional measurements followed by cardiac harvest. Both OHC and OHCM animals developed significantly greater weight gain, total cholesterol, and LDL:HDL ratio compared to OC controls. Metforminadministration reversed diet-induced hypertension and glucose intolerance. There were no differences in global and regional contractility, myocardial perfusion, capillary and arteriolar density, or total protein oxidation between groups. Myocardial protein expression of VEGF, PPAR-α, c, and d was significantly increased in the OHC and OHCM groups. Microvessel reactivity was improved in the OHC and OHCM groups compared to controls, and correlated with increased p-eNOS expression. Overfed Ossabaw miniswine develop several components of metabolic syndrome. However, impairments of myocardial function, neovascularization and perfusion were not present, and microvessel reactivity was paradoxically improved in hypercholesterolemic animals. The observed cardioprotection despite metabolic derangements may be due to lipid-dependant upregulation of the PPAR pathway which is anti-inflammatory and governs myocardial fatty acid metabolism.

KW - Cardioprotection

KW - Chronic ischemia

KW - Metabolic syndrome

KW - Ossabaw

UR - http://www.scopus.com/inward/record.url?scp=84859713764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859713764&partnerID=8YFLogxK

U2 - 10.1007/s00395-012-0243-y

DO - 10.1007/s00395-012-0243-y

M3 - Article

VL - 107

JO - Basic Research in Cardiology

JF - Basic Research in Cardiology

SN - 0300-8428

IS - 2

M1 - 0243

ER -