Subject(s)
Cardiovascular System , Hypertension , Vascular Stiffness , Blood Pressure , Humans , Thyroid HormonesABSTRACT
Introduction: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular calcium (Ca2+) release channels located on the endoplasmic/sarcoplasmic reticulum. The availability of the structure of the ligand-binding domain of IP3Rs has enabled the design of compatible ligands, but the limiting step remains their actual effectiveness in a biological context.Areas covered: This article summarizes the compelling literature on both agonists and antagonists targeting IP3Rs, emphasizing their strengths and limitations. The main challenges toward the discovery and development of IP3 receptor modulators are also described.Expert opinion: Despite significant progress in recent years, the pharmacology of IP3R still has major drawbacks, especially concerning the availability of specific antag onists. Moreover, drugs specifically targeting the three different subtypes of IP3R are especially needed.
Subject(s)
Calcium , Calcium/metabolism , Humans , Inositol 1,4,5-Trisphosphate Receptors , LigandsABSTRACT
The potential beneficial effects of the antioxidant properties of vitamin C have been investigated in a number of pathological conditions. In this review, we assess both clinical and preclinical studies evaluating the role of vitamin C in cardiac and vascular disorders, including coronary heart disease, heart failure, hypertension, and cerebrovascular diseases. Pitfalls and controversies in investigations on vitamin C and cardiovascular disorders are also discussed.
Subject(s)
Bone Density/drug effects , Calcium, Dietary/adverse effects , Cardiovascular Diseases/chemically induced , Dietary Supplements/adverse effects , Osteoporosis, Postmenopausal/prevention & control , Vascular Calcification/chemically induced , Adult , Aged , Calcitonin/blood , Calcium/blood , Cardiovascular Diseases/epidemiology , Cardiovascular System/drug effects , Drug Interactions , Female , Humans , Male , Meta-Analysis as Topic , Middle Aged , Myocardial Infarction/chemically induced , Myocardial Infarction/epidemiology , Nutritional Requirements , Observational Studies as Topic , Parathyroid Hormone/blood , Vitamin D/administration & dosage , Vitamin D/pharmacokineticsABSTRACT
The inclusion of microRNAs (miRNAs) in extracellular microvesicles/exosomes (named cardiosomes when deriving from cardiomyocytes) allows their active transportation and ensures cell-cell communication. We hypothesize that cardiosomal miRNAs play a pivotal role in the activation of myofibroblasts following ischemic injury. Using a murine model of myocardial infarction (MI), we tested our hypothesis by measuring in isolated fibroblasts and cardiosomes the expression levels of a set of miRNAs, which are upregulated in cardiomyocytes post-MI and involved in myofibroblast phenoconversion. We found that miR-195 was significantly upregulated in cardiosomes and in fibroblasts isolated after MI compared with SHAM conditions. Moreover, primary isolated cardiac fibroblasts were activated both when incubated with cardiosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post-MI cardiomyocytes, whereas no significant effect was observed following incubation with cardiosomes or medium from sham cardiomyocytes. Taken together, our findings indicate for the first time that a cardiomyocyte-specific miRNA, transferred to fibroblasts in form of exosomal cargo, is crucial in the activation of myofibroblasts.
