Altered melusin pathways involved in cardiac remodeling following acute myocardial infarction.

Abstract

BACKGROUND:

Melusin, a muscle-specific integrin-linked protein, has been reported to be a biomechanical sensor and to protect the heart from pressure overload. In the present study, we investigated the possible role that melusin plays during cardiac remodeling after myocardial infarction (MI).

METHODS:

We constructed a heart failure model of rats induced by left anterior descending coronary artery ligation. At different time points (1, 2, 3, 4, 6, and 8 weeks) following the operation, cardiac function was monitored by echocardiography and hemodynamic assessment; cardiac morphology was measured using hematoxylin-eosin-stained sections. Melusin expression, as well as p-Akt, Akt, and one of the Rho small GTPase family members, CDC42, was determined dynamically by Western blotting analysis during the postinfarction cardiac remodeling.

RESULTS:

Progressive increase in left ventricular (LV) end-systolic dimension and LV end-diastolic dimension and decrease in percent LV fractional shortening (%FS) and LVdp/dt(max) demonstrated gradually deteriorated cardiac function in rats following MI operation. Morphological analysis revealed cardiac remodeling in MI animals, including increased LV diameter and decreased border zone thickness. We also showed a dynamic change in melusin during heart failure progression; it had an initial decline which was evident at 3 weeks and increased subsequently, reaching peak levels at 6 weeks. This dynamic change in melusin was significantly correlated with %FS and LVdp/dt(max.) p-Akt/Akt and CDC42 protein expression was correlated with melusin content.

CONCLUSIONS:

The altered melusin pathways and CDC42 parallel the cardiac function progression during cardiac remodeling post-MI. The dynamic change of them during this procedure may represent an important molecular mechanism underlying postinfarction cardiac remodeling and provide potential therapeutic targets.

• Authors: Rong Gu, Di Zheng, Jian Bai, Jun Xie, Qing Dai, Biao Xu
• Journal: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology (Cardiovasc Pathol) 2012 Mar-Apr Vol. 21 Issue 2 Pg. 105-11 ISSN: 1879-1336 [Electronic] United States
• PMID: 21546274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cytoskeletal Proteins
• ITGB1BP2 protein, human
• Muscle Proteins
• cdc42 GTP-Binding Protein

Topics

• Animals
• Body Weight
• Cytoskeletal Proteins (metabolism)
• Disease Models, Animal
• Echocardiography
• Heart Failure (metabolism, pathology, physiopathology)
• Hemodynamics
• Male
• Muscle Proteins (metabolism)
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Ventricular Remodeling (physiology)
• cdc42 GTP-Binding Protein (metabolism)