Related Experiment Videos
Molecular mechanisms of myocardial remodeling
1Institut National de la Sante et de la Recherche Medicale U. 127, Hopital Lariboisiere, Paris, France.
Insights
Cardiac remodeling (CR) involves permanent changes after myocardial infarction or hypertension, particularly in older adults. Key factors include fibrosis, cell death, and genetic expression alterations, leading to heart failure and arrhythmias.
Area of Science:
- Cardiology
- Pathophysiology
- Geriatrics
Background:
- Cardiac remodeling (CR) involves structural and functional changes in the heart.
- It is often secondary to myocardial infarction (MI) and/or arterial hypertension.
- CR is particularly prevalent and significant in the aging (senescent) heart.
Purpose of the Study:
- To review permanent modifications in cardiac remodeling.
- To focus on clinical dysfunction related to CR, especially in the context of MI, hypertension, and aging.
- To explore the biological and clinical aspects of CR.
Main Methods:
- Review of existing literature on cardiac remodeling.
- Analysis of biological mechanisms driving CR, including adaptation, fibrosis, and cell death.
- Examination of clinical manifestations and markers of CR.
Main Results:
- CR is characterized by myocyte and collagen network adaptation, ventricular fibrosis, and cell death (necrosis, apoptosis).
- Genetic expression changes include hypertrophy, altered myosin and ATPase, and modified hormonal systems.
- Fibrosis is a key marker for heart failure, impacting diastolic stiffness and arrhythmia susceptibility.
Conclusions:
- Cardiac remodeling involves complex biological processes with significant clinical consequences.
- Fibrosis, altered gene expression, and cellular changes contribute to heart failure and arrhythmias.
- Understanding CR is crucial, especially in the elderly population, for managing cardiovascular dysfunction.
Abstract:
"Remodeling" implies changes that result in rearrangement of normally existing structures. This review focuses only on permanent modifications in relation to clinical dysfunction in cardiac remodeling (CR) secondary to myocardial infarction (MI) and/or arterial hypertension and includes a special section on the senescent heart, since CR is mainly a disease of the elderly. From a biological point of view, CR is determined by 1 ) the general process of adaptation which allows both the myocyte and the collagen network to adapt to new working conditions; 2) ventricular fibrosis, i.e., increased collagen concentration, which is multifactorial and caused by senescence, ischemia, various hormones, and/or inflammatory processes; 3) cell death, a parameter linked to fibrosis, which is usually due to necrosis and apoptosis and occurs in nearly all models of CR. The process of adaptation is associated with various changes in genetic expression, including a general activation that causes hypertrophy, isogenic shifts which result in the appearance of a slow isomyosin, and a new Na+-K+-ATPase with a low affinity for sodium, reactivation of genes encoding for atrial natriuretic factor and the renin-angiotensin system, and a diminished concentration of sarcoplasmic reticulum Ca2+-ATPase, beta-adrenergic receptors, and the potassium channel responsible for transient outward current. From a clinical point of view, fibrosis is for the moment a major marker for cardiac failure and a crucial determinant of myocardial heterogeneity, increasing diastolic stiffness, and the propensity for reentry arrhythmias. In addition, systolic dysfunction is facilitated by slowing of the calcium transient and the downregulation of the entire adrenergic system. Modifications of intracellular calcium movements are the main determinants of the triggered activity and automaticity that cause arrhythmias and alterations in relaxation.