ABSTRACT
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder that associates with nucleotide sequence variants in genes encoding sarcomere related proteins, and is recognized as the most common heritable cardiac diseases. Clinically, HCM can be extremely variable and this makes the diagnosis difficult until the development of serious or fatal events. Nevertheless, the main hallmark of HCM is represented by left ventricle hypertrophy that can be occasionally associated to cardiac arrhythmias, chest pain, diastolic dysfunction, obstruction of left ventricular outflow tract. The present review aims to focus on the complex interplay existing between the multifaceted non-genetic molecular mechanisms underlying HCM onset and progression, and the key pathophysiological role of abnormal coronary artery function. As the clinical course of HCM shows a mortality rate per year up to 6% the importance of innovative therapeutic strategies will be discussed, especially in regard to the use of potential endogenous coronary modulators to be enrolled as modifiers of HCM phenotype.
Subject(s)
Cardiomyopathy, Hypertrophic , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/drug therapy , Cardiomyopathy, Hypertrophic/genetics , Heart , Humans , Hypertrophy, Left Ventricular , Phenotype , Sarcomeres/genetics , Sarcomeres/metabolismABSTRACT
The cardiac function critically depends on an adequate myocardial oxygenation and on a correct coronary blood flow. Endothelial, hormonal and extravascular factors work together generating a fine balance between oxygen supply and oxygen utilization through the coronary circulation. Among the regulatory factors that contribute to the coronary tone, increasing attention is paid to the cardiac endocrines, such as chromogranin A, a prohormone for many biologically active peptides, including vasostatin and catestatin. In this review, we will summarize the available evidences about the coronary effects of these molecules, and their putative mechanism of action. Laboratory and clinical data on chromogranin A and its derived fragments will be analyzed in relation to the scenario of the endocrine heart, and of its putative clinical perspectives.
Subject(s)
Chromogranin A/pharmacology , Coronary Circulation/physiology , Endothelium, Vascular/metabolism , Myocardial Contraction/physiology , Animals , Chromogranin A/metabolism , Coronary Circulation/drug effects , Endothelium, Vascular/drug effects , Humans , Myocardial Contraction/drug effects , Peptide Fragments/metabolism , Peptide Fragments/pharmacologyABSTRACT
BACKGROUND: Research on Chromogranin A (CGA) and its derived fragments convincingly demonstrated the multifunctional activity of the 21 amino acid peptide named Catestatin (CST: human CGA352-372, bovine CGA344-364, rat CGA367-387). This review aims to provide a synopsis of the current information concerning the biological role of CST in health and disease. METHODS: Structured search of bibliographic databases for peer-reviewed research literature. RESULTS: CST is mainly known as an inhibitor of the nicotinic-dependent Catecholamine (CA) release, and an anti-hypertensive peptide, but its role includes a modulation of antioxidant and immune defense, epidermal function, and adipose tissue homeostasis. CST influences the cardiocirculatory system acting both indirectly, via the autonomic nervous system, and directly by influencing the basal cardiac function, and the stretch-dependent myocardial performance. It also counteracts the effects of adrenergic stimulation on the heart and protects the myocardium from ischemia/reperfusion (I/R) injury, acting in pre- and postconditioning protection. CONCLUSIONS: The knowledge on CST is constantly expanding, thanks to a growing number of human studies that document its involvement in physiological modulation and in many severe diseases, also revealing its applicative potential as a clinical biomarker.
Subject(s)
Chromogranin A/metabolism , Peptide Fragments/metabolism , Animals , Cardiovascular Diseases/drug therapy , Central Nervous System/drug effects , Central Nervous System/metabolism , Chromogranin A/chemistry , Chromogranin A/pharmacology , Chromogranin A/therapeutic use , Heart/drug effects , Humans , Immunity, Innate/drug effects , Myocardium/metabolism , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Peptide Fragments/therapeutic use , Plasmodium/drug effects , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Morpho-dynamic aspects of the frog (Rana esculenta) heart were correlated to seasonal and sexual traits. The statistical analysis of the data (696 frog specimens: 448 males and 248 females), collected during 8 years of routine research on frog cardiac physiology, indicated that cardiac biology is characterised by sexual dimorphism. The relative cardiac weight of males was higher than that of females of similar size. With respect to the males of similar size, female frogs revealed an increased relative ventricular weight and ventricular contractile capacity. The morphometric analysis showed that the ventricular growth was achieved through significant myocardial enlargement accompanied by a reduction of the lacunary spaces. This is more pronounced in females during the breeding period. The correlation between sexual maturity and ventricular morpho-functional changes revealed that in male frogs sexual maturity correlates with a remarkable increment of the ventricular weight associated with higher values of pulse pressure. This data indicate that sex and season-related factors influence cardiac morpho-dynamics in R. esculenta.
