Related Experiment Video
Updated: Aug 10, 2026
A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats
Published on: December 2, 2016
Effect of long-term hyperhomocysteinemia on myocardial structure and function in hypertensive rats
Sulochana Devi1, Richard H Kennedy, Lija Joseph
1Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Insights
High homocysteine levels accelerate hypertensive heart disease progression to systolic dysfunction, driven by increased myocardial oxidant stress. Early dietary intervention can partially mitigate these adverse cardiac effects.
Area of Science:
- Cardiovascular Science
- Metabolic Disease Research
- Toxicology
Background:
- Mechanisms of hyperhomocysteinemia (Hhe) overlap with adverse cardiac remodeling pathways.
- Investigated the hypothesis that Hhe promotes myocardial fibrosis and systolic dysfunction.
Purpose of the Study:
- To determine if hyperhomocysteinemia (Hhe) accelerates hypertensive heart disease progression.
- To elucidate the role of myocardial oxidant stress in Hhe-induced cardiac dysfunction.
Main Methods:
- Spontaneously hypertensive rats (SHRs) received control, Hhe-inducing, or combined diets.
- Assessed plasma homocysteine, blood pressure, cardiac remodeling, oxidative stress, and in vitro cardiac function.
Main Results:
- Hhe induced interstitial fibrosis and increased myocardial oxidant stress.
- Systolic function was significantly depressed in Hhe animals.
- Dietary intervention partially prevented these changes.
Conclusions:
- Clinically relevant Hhe accelerates hypertensive heart disease to systolic dysfunction.
- Increased myocardial oxidant stress is implicated in this process.
- Findings have significant clinical implications due to high prevalence of hypertension and Hhe.
Background:
Postulated mechanisms of hyperhomocysteinemia (Hhe) overlap with proposed mechanisms of adverse cardiac remodeling such as altered collagen metabolism and oxidant stress. Hence we examined the hypothesis that Hhe would promote myocardial fibrosis and systolic dysfunction.
Methods:
Three-month-old spontaneously hypertensive rats (SHRs) were divided into three groups: (1) control, given amino-acid defined diet for 20 weeks; (2) Hhe group, given Hhe-inducing diet for 20 weeks; and (3) combined diet group, which were given Hhe-inducing diet for 10 weeks (which leads to myocardial fibrosis and diastolic dysfunction as shown in our prior studies) and subsequently returned to amino acid-defined diet for 10 more weeks. At the end of the treatment period, plasma homocysteine (Hcy) levels and blood pressure were measured, and hearts were isolated for histomorphometric and biochemical assessment of cardiac remodeling and myocardial oxidative stress, and for in vitro cardiac function studies.
Results:
The Hhe animals demonstrated a significant increase in the ratio of collagenous to noncollagenous protein due to reactive interstitial fibrosis, and increased myocardial oxidant stress, compared to the control group. Systolic function was significantly depressed in the Hhe animals compared to the control group. These changes were partially prevented by return to control diet at 10 weeks.
Conclusions:
Our results demonstrate that clinically relevant levels of Hhe accelerate progression of hypertensive heart disease to systolic dysfunction and that increased myocardial oxidant stress may play a role in this process. Considering the high prevalence of hypertension and Hhe in the general population, our findings may have great clinical significance.
Related Concept Videos
01:29Heart Failure II: Pathophysiology
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:21Myocarditis I: Introduction
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...