Osteopontin-mediated myocardial fibrosis in heart failure: a role for lysyl oxidase?

Aims: We investigated whether the pro-fibrotic matricellular protein osteopontin (OPN) is associated with the enzymes involved in the extracellular synthesis of fibril-forming collagen type I (i.e. procollagen C-proteinase, PCP) and its cross-linking to form insoluble fibrils (i.

Glucagon-like peptide 1 and cardiac cell survival.

During myocardial infarction (MI), a variety of mechanisms contribute to activation of cell death processes in cardiomyocytes, which determines the final MI size, subsequent mortality, and post-MI remodeling. The deleterious mechanisms activated during the ischemia and reperfusion phases in MI include oxygen deprival, decreased availability of nutrients and survival factors, accumulation of waste products, generation of oxygen free radicals, calcium overload, neutrophil infiltration in the ischemic area, depletion of energy stores, and opening of the mitochondrial permeability transition pore, all of them contributing to activation of apoptosis and necrosis in cardiomyocytes. Glucagon-like peptide-1 [GLP-1 (7-36) amide] has gained relevance in recent years for metabolic treatment of patients with type 2 diabetes mellitus.

GLP-1 and cardioprotection: from bench to bedside.

During myocardial infarction (MI), a variety of mechanisms contribute to the activation of cell death processes in cardiomyocytes, determining the final MI size, subsequent mortality, and post-MI remodelling. The deleterious mechanisms accompanying the ischaemic and reperfusion phases in MI include deprivation of oxygen, nutrients, and survival factors, accumulation of waste products, generation of oxygen free radicals, calcium overload, neutrophil infiltration of the ischaemic area, depletion of energy stores, and opening of the mitochondrial permeability transition pore, all of which contribute to the activation of apoptosis and necrosis in cardiomyocytes. During the last few years, glucagon-like peptide-1 (GLP-1) (7-36)-based therapeutic strategies have been incorporated into the treatment of patients with type 2 diabetes mellitus.

Cardiotrophin-1 in hypertensive heart disease.

Hypertensive heart disease, here defined by the presence of pathologic left ventricular hypertrophy in the absence of a cause other than arterial hypertension, is characterized by complex changes in myocardial structure including enhanced cardiomyocyte growth and non-cardiomyocyte alterations that induce the remodeling of the myocardium, and ultimately, deteriorate left ventricular function and facilitate the development of heart failure. It is now accepted that a number of pathological processes mediated by mechanical, neurohormonal, and cytokine routes acting on the cardiomyocyte and the non-cardiomyocyte compartments are responsible for myocardial remodeling in the context of arterial hypertension. For instance, cardiotrophin-1 is a cytokine member of the interleukin-6 superfamily, produced by cardiomyocytes and non-cardiomyocytes in situations of biomechanical stress that once secreted interacts with its receptor, the heterodimer formed by gp130 and gp90 (also known as leukemia inhibitory factor receptor beta), activating different signaling pathways leading to cardiomyocyte hypertrophy, as well as myocardial fibrosis.

Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes.

Activation of apoptosis contributes to cardiomyocyte dysfunction and death in diabetic cardiomyopathy. The peptide glucagon-like peptide-1 (GLP-1), a hormone that is the basis of emerging therapy for type 2 diabetic patients, has cytoprotective actions in different cellular models. We investigated whether GLP-1 inhibits apoptosis in HL-1 cardiomyocytes stimulated with staurosporine, palmitate, and ceramide.

Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexin A5.

Aims: Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5.

Cardiovascular translational medicine (III). Genomics and proteomics in heart failure research.

Heart failure is a complex syndrome and is one of the main causes of morbidity and mortality in developed countries. Despite considerable research effort in recent years, heart failure prevention and treatment strategies still suffer significant limitations. New theoretical and technical approaches are, therefore, required.

Biochemical markers of myocardial remodelling in hypertensive heart disease.

The intricate mechanisms responsible for the structural remodelling of the myocardium that facilitates the evolution to heart failure in hypertensive patients, namely in those with left ventricular hypertrophy, requires from clinicians the utilization of a multibiomarker approach for short-term and long-term stratification as well as prognostication of patients. Biochemical markers may also help to identify patients with no clinical evidence of hypertensive heart disease, and provide information about the need for more aggressive therapy during different stages of the disease, and potentially provide valuable biochemical data for the specialist. Although there is a continuous and complex interplay between biochemical and imaging markers, perhaps their use will also have the potential to modify the medical management of patients with hypertensive heart disease and therapeutic decision-making by tailoring a targeted therapy according to the predominant mechanism of myocardial remodelling.