calpain has been researched along with Cardiovascular-Diseases* in 7 studies
3 review(s) available for calpain and Cardiovascular-Diseases
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An update on the therapeutic potential of calpain inhibitors: a patent review.
Calpain is a cytosolic proteinase that regulates of a wide range of physiological functions. The enzyme has been implicated in various pathological conditions including neurodegenerative disorders, cardiovascular disorders, cancer, and several other diseases. Therefore, calpain inhibitors are of interest as therapeutic agents and have been studied in preclinical models of several diseases in which the enzyme has been implicated.. Calpain inhibitors that were disclosed over the last 5 years (2015-2019) include calpastatin-based peptidomimetics; thalassospiramide lipopeptides; disulfide analogs of alpha-mercaptoacrylic acids; allosteric modulators; azoloimidazolidenones; and macrocyclic/non-macrocyclic carboxamides. The effectiveness of some of the inhibitors in preclinical animal models is discussed.. Significant milestones that were made over this time frame include: a) disclosure of novel blood-brain barrier (BBB) permeable calpastatin analogs as calpain inhibitors; b) disclosure that potent calpain inhibitors can be obtained by targeting the hydrophobic pockets on chain A of PEF(S) of the small subunit of calpain; c) use of PEF(S) (PDB ID: 4WQ2) in virtual screening to identify novel structurally diverse calpain inhibitors; and d) mitigation of the metabolic instability of the alpha-ketoamide warhead of calpain inhibitors. Topics: Animals; Calpain; Cardiovascular Diseases; Drug Development; Glycoproteins; Humans; Neoplasms; Neurodegenerative Diseases; Patents as Topic; Peptidomimetics | 2020 |
[The physiological and pathological function of Ca(2 +) -dependent cysteine protease (Calpain) ].
Calpains are Ca(2 +) -dependent cysteine proteases. Fifteen gene products of calpains are expressed in mammals. Among them, Calpain 1 and Calpain 2 are ubiquitously expressed and have been investigated extensively. Under the physiological conditions, calpain activity is strictly regulated by endogenous inhibitory protein, Calpastatin. Calpains are activated in the various cardiovascular diseases and implicated in their pathogenesis by degrading numerous target proteins. Here we briefly summarize the physiological and pathological role of calpains in the cardiovascular diseases. Topics: Animals; Calcium; Calcium-Binding Proteins; Calpain; Cardiovascular Diseases; Genetic Predisposition to Disease; Humans | 2013 |
Regulation and physiological roles of the calpain system in muscular disorders.
Calpains, a family of Ca(2+)-dependent cytosolic cysteine proteases, can modulate their substrates' structure and function through limited proteolytic activity. In the human genome, there are 15 calpain genes. The most-studied calpains, referred to as conventional calpains, are ubiquitous. While genetic studies in mice have improved our understanding about the conventional calpains' physiological functions, especially those essential for mammalian life as in embryogenesis, many reports have pointed to overactivated conventional calpains as an exacerbating factor in pathophysiological conditions such as cardiovascular diseases and muscular dystrophies. For treatment of these diseases, calpain inhibitors have always been considered as drug targets. Recent studies have introduced another aspect of calpains that calpain activity is required to protect the heart and skeletal muscle against stress. This review summarizes the functions and regulation of calpains, focusing on the relevance of calpains to cardiovascular disease. Topics: Animals; Calpain; Cardiovascular Diseases; Enzyme Activation; Humans; Muscle, Skeletal; Muscular Diseases; Myocardium | 2012 |
4 other study(ies) available for calpain and Cardiovascular-Diseases
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Epigenome-Wide Association Study for All-Cause Mortality in a Cardiovascular Cohort Identifies Differential Methylation in Castor Zinc Finger 1 (
Background DNA methylation is implicated in many chronic diseases and may contribute to mortality. Therefore, we conducted an epigenome-wide association study (EWAS) for all-cause mortality with whole-transcriptome data in a cardiovascular cohort (CATHGEN [Catheterization Genetics]). Methods and Results Cases were participants with mortality≥7 days postcatheterization whereas controls were alive with≥2 years of follow-up. The Illumina Human Methylation 450K and EPIC arrays (Illumina, San Diego, CA) were used for the discovery and validation sets, respectively. A linear model approach with empirical Bayes estimators adjusted for confounders was used to assess difference in methylation (Δβ). In the discovery set (55 cases, 49 controls), 25 629 (6.5%) probes were differently methylated ( Topics: Aged; Calpain; Cardiovascular Diseases; Case-Control Studies; Chloride-Bicarbonate Antiporters; CpG Islands; DNA Methylation; DNA Probes; DNA-Binding Proteins; Epigenome; Female; Follow-Up Studies; Gene Expression Profiling; Genome-Wide Association Study; Humans; Male; Muscle Proteins; Nuclear Receptor Co-Repressor 2; Protein Isoforms; Proto-Oncogene Proteins pp60(c-src); RNA, Messenger; Transcription Factors | 2019 |
Luteolin inhibits lysophosphatidylcholine-induced apoptosis in endothelial cells by a calcium/mitocondrion/caspases-dependent pathway.
Luteolin, a naturally occurring polyphenol flavonoid, has demonstrated some beneficial modulation toward the endothelium. This study aims to investigate the effects of luteolin on lysophosphatidylcholine (LPC)-induced apoptosis, a key event in the pathogenesis of atherosclerosis, in endothelial cells. Luteolin reduced not only LPC-induced cell death but also lactate dehydrogenase (LDH) leakage. Luteolin inhibition of LPC-induced apoptosis in endothelial cells demonstrated its protection against the cytotoxicity of LPC. LPC-induced apoptosis is characterized by a calcium-dependent mitochondrial pathway, involving calcium influx, activation of calpains, cytochrome C release and caspases activation. Luteolin reduced calcium influx. It also inhibited calpains activation and prevented the release of cytochrome C from mitochondrion. The inhibition of cytochrome C release by luteolin blocked the activation of caspase-3 and thus prevented subsequent endothelial cell apoptosis. These results suggested that luteolin inhibits LPC-induced apoptosis in endothelial cells through the blockage of the calcium-dependent mitochondrial pathway. Topics: Apoptosis; Calcium; Calpain; Cardiovascular Diseases; Caspase Inhibitors; Caspases; Endothelial Cells; Enzyme Activation; Humans; L-Lactate Dehydrogenase; Luteolin; Lysophosphatidylcholines; Metabolic Networks and Pathways; Mitochondria | 2010 |
Elevated calcium level induces calcium-dependent proteolysis of A-CAM (N-cadherin) in heart--analysis by detergent-treated model.
Calcium overload induces cardiac muscle cell dysfunction in cardiovascular diseases. We investigated the effects of elevated calcium level on adherens-junction-specific cell adhesion molecule (A-CAM). Incubation of Triton X-100-treated canine heart homogenate in the presence of Ca2+ reduced the content of A-CAM. Reduction in A-CAM requires milli-molar Ca2+ and was inhibited by protease inhibitors, leupeptin and calpeptin. Immunohistochemical observation revealed that m-calcium-activated neutral protease (m-CANP) was colocalized with A-CAM in intercalated disks. These data suggested that m-CANP proteolyzes A-CAM in response to calcium overload in cardiac muscle. Topics: Animals; Cadherins; Calcium; Calpain; Cardiovascular Diseases; Dogs; Fluorescent Antibody Technique, Indirect; Myocardium; Octoxynol | 1995 |
[Cardiovascular diseases and enzyme inhibitors].
Topics: Animals; Blood Platelets; Calpain; Cardiovascular Diseases; Endothelins; Humans; Piperazines; Platelet Aggregation Inhibitors; Serotonin | 1991 |