"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.

Increasing evidence suggests that mineralo-and glucocorticoids modulate cardiovascular homeostasis via the effects of circulating components generated within the adrenals but also through local synthesis. The aim of this study was to assess the existence of such a steroidogenic system in heart.Using the quantitative reverse transcriptase-polymerase chain reaction, the terminal enzymes of corticosterone and aldosterone synthesis (11␤-hydroxylase and aldosterone synthase, respectively) were detected in the rat heart. This pathway was shown to be physiologically active, since production of aldosterone, corticosterone, and their precursor, deoxycorticosterone, was detected in both the homogenate and perfusate of isolated rat hearts using radioimmunoassay after Celite column chromatography. Perfusion of angiotensin II or adrenocorticotropin for 3 h increased aldosterone and corticosterone production and decreased deoxycorticosterone, suggesting that aldosterone and corticosterone are formed within the isolated heart from a locally present substrate.Chronic regulation of this intracardiac system was then examined. As in adrenals cardiac 11␤-hydroxylase and aldosterone-synthase mRNAs were independently regulated by 1 week's treatment with either low sodium and high potassium diet (which increased aldosterone synthase mRNA level only), angiotensin II (which raised level of both mRNAs), or adrenocorticotropin (which stimulated the 11␤-hydroxylase gene exclusively). Changes in cardiac steroid levels during treatment were not directly related to their plasma levels suggesting independent regulating mechanisms. This study, therefore, provides the first evidence for the existence of an endocrine cardiac steroidogenic system in rat heart and emphasizes its potential physiological and pathological relevance.Glucocorticoids (corticosterone in the rat and cortisol in humans) and mineralocorticoids (mainly aldosterone in both species) are synthesized from cholesterol, predominantly in the adrenal cortex. The two forms of the cytochrome P-450 enzyme which catalyze the final step of these synthetic pathways are encoded by two closely related genes CYP11B1 and CYP11B2, respectively (1) but display differences in their enzymatic activity, regulation, and tissular distribution (2). P-450 11␤-hydroxylase (11␤-OHase) 1 synthesizes corticosterone from 11-deoxycorticosterone (DOC) in the zona fasciculata reticularis and is mainly regulated by adrenocorticotropic hormone (ACTH). P-450 aldosterone (Aldo)-synthase, which catalyzes synthesis of aldosterone from DOC, is present only in the zona glomerulosa. Its activity is principally controlled by angiotensin II (Ang II) and potassium and more weakly by ACTH and sodium (3, 4). While ACTH is a chronic inhibitor of aldosterone secretion, it is also a potent stimulator of its synthesis in some acute conditions (5, 6). Two other P-450c11 genes, CYP11B3 and CYP11B4 were recently cloned from a rat genomic library (7). CYP11B3 was 97% identical to CYP11B1 and encoded an enzyme with activities interm...

The goal of this review is to summarize our knowledge of the plasticity of striated muscles in terms of contractile proteins. During development or when the working conditions are changed, the intrinsic physiological properties of both cardiac and skeletal muscles are modified. These modifications generally adapt the muscle to the new environmental requirements. One of the best examples is compensatory overload obtained in fast skeletal muscle by synergistic tenotomy and in a fast ventricle, such as in rats, by aortic banding. In both cases, after a few weeks the initial speed of shortening for the unloaded muscle drops, whereas the maximum tension developed remains unchanged. Heat measurements show that efficiency (i.e., g work/mol ATP) is improved at the fiber level. The fast skeletal muscle becomes slow, fatigue resistant, and then more adapted to endurance. For the ventricle as a whole to become slow is beneficial only if one contraction is considered; however, it is detrimental in terms of cardiac output and leads finally to failure. This adaptational process is partly explained by quantitative and qualitative changes in contractile proteins. Protein synthesis is rapidly enhanced and muscles hypertrophy, which in turn multiplies the contractile units and for the cardiac cylinder normalizes the wall stress. In the meantime the structure and, for myosin, the biological activity of several contractile proteins are modified. These modifications are very unlikely to be posttranscriptional and are in fact explained by several isoform shifts. In both tissues, for example, the expression of the gene coding for a fast myosin (MHCf in skeletal muscle, alpha-MHC in ventricles) is repressed and that of the gene coding for a slow myosin (beta-MHC in both tissues) is stimulated. This is accompanied by a coordinated increase in synthesis of other contractile proteins and, in skeletal muscle only, by isoform shifts of myosin light chains and of the TM-TN regulatory system. Other changes are less well understood. During development it has recently been discovered that three different MHCs (MHCemb, MHCneo, and MHCf) appear sequentially in fast skeletal muscle, which explains, for example, several contradictions of immunological cross-reactions. Currently, however, the functional significance of this finding is unknown, and the well-known decrease of shortening velocity observed in cardiac and skeletal muscles during fetal life is unexplained in terms of contractile proteins.(ABSTRACT TRUNCATED AT 400 WORDS)