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Effects of angiotensin receptor blockade on haemodynamics and gene expression after myocardial infarction
Andrey K Gurevich1, Sandor A Falk, Raphael A Nemenoff
1Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Insights
Valsartan treatment preserved cardiac function and reversed gene expression changes after myocardial infarction (MI) in rats. This study highlights the protective role of angiotensin receptor blockade in mitigating heart failure progression.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Congestive heart failure (CHF) is a prevalent disease with poorly understood molecular mechanisms of cardiac dysfunction.
- The angiotensin system is implicated in cardiac injury, but its precise role remains unclear.
Purpose of the Study:
- To investigate the relationship between hemodynamic and molecular events in cardiac dysfunction post-myocardial infarction (MI).
- To examine the role of the angiotensin system in these processes using valsartan, an angiotensin receptor blocker.
Main Methods:
- Rats underwent MI induction via coronary artery ligation.
- Hemodynamic parameters were assessed using echocardiography.
- Gene expression profiles were analyzed using Affymetrix Genechip oligonucleotide arrays post-MI.
Main Results:
- Valsartan preserved cardiac contractility and prevented left ventricular (LV) dilatation and hypertrophy compared to untreated controls.
- MI induced significant changes in gene expression related to muscle function, fibrosis, and immune response.
- Valsartan treatment reversed a substantial proportion of these MI-induced gene expression alterations.
Conclusions:
- Angiotensin receptor blockade with valsartan demonstrates a protective effect on cardiac function following MI.
- This cardioprotection is associated with a reversal of MI-induced changes in gene expression patterns.
Introduction:
Despite the fact that congestive heart failure (CHF) remains the most common disease in the developed world and has been extensively studied, there is little known about the molecular and cellular mechanisms of cardiac dysfunction. Angiotensin has been implicated as a mediator of cardiac injury; however, the mechanisms of its action have not been delineated. The objective of this study was to examine the relationship between the haemodynamic and molecular events during cardiac dysfunction and the role of the angiotensin system.
Study Design:
We examined the effects of the angiotensin receptor blocker, valsartan, on changes in the haemodynamic and gene expression patterns in a postmyocardial infarction model in the rat.
Methods:
Myocardial infarction (MI) was induced in rats by coronary artery ligation. Cardiac haemodynamics were monitored using echocardiography. Gene expression profiles after myocardial infarction were identified using Affymetrix Genechip oligonucleotide arrays.
Results:
Myocardial contractility, as assessed by cardiac output and left ventricle (LV) fraction of shortening, was reduced in untreated animals by week 3 after MI (p < 0.05 versus baseline), and preserved with valsartan treatment as observed by the nonsignificant changes versus baseline. LV dilatation, as demonstrated by increases in LV systolic and diastolic diameters, developed by week 3 in untreated animals (p < 0.05 versus baseline) while valsartan-treated animals were protected and showed no significant increases in diameter size compared with baseline. LV hypertrophy, as shown by LV posterior wall thickness, was more profound in untreated animals (p < 0.05 versus baseline) than in those treated with valsartan at weeks 3 and 4. Changes in gene expression at 4 weeks after MI included those encoding muscle-specific genes, fibrous tissue proliferation, immune response and various others. Treatment with valsartan reversed these changes in 67% of overexpressed genes and 83% of underexpressed genes.
Conclusion:
Angiotensin receptor blockade with valsartan was found to protect cardiac function, and this beneficial effect was accompanied by a reversal of changes in gene expression induced by MI.
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