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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heart disease is a leading cause of death in newborns and in adults. Efforts to promote cardiac repair by introduction or recruitment of exogenous stem cells hold promise but typically involve isolation and introduction of autologous or donor progenitor cells. We have found that the G-actin-sequestering peptide thymosin beta4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin beta4. We found that thymosin beta4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt/PKB, which was necessary for thymosin beta4's effects on cardiomyocytes. After coronary artery ligation in mice, thymosin beta4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival, and improved cardiac function. These findings suggest that thymosin beta4 promotes cardiomyocyte and endothelial migration, survival, and repair and may be a novel therapeutic target in the setting of acute myocardial damage.
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PMID:Thymosin beta4 is cardioprotective after myocardial infarction. 1760 Feb 80

Cardiac hypertrophy is a significant independent risk factor for increased mortality, comprising of maladaptive changes in cellular, molecular and metabolic processes that ultimately lead to heart failure. However, cardiac hypertrophy represents a continuum from physiological to compensatory to pathological hypertrophy, so that treatment modalities aimed to shift hypertrophy towards the physiological phenotype would represent an attractive therapeutic strategy. Many of the physiological changes caused by thyroid hormone (TH) treatment may provide direct benefit to the failing heart. Recent experimental studies have shown that TH rapidly activates pro-survival PKB/Akt-mTOR signaling pathways, thus providing cytoprotection and increasing synthesis of normal contractile proteins and metabolic enzymes. TH induces a normal physiological phenotype by binding to nuclear TH receptors that regulate expression of specific genes which promote cell survival and enhance contractile function. Physiological cardiac growth occurs with a coordinated angiogenic response that normalizes myocardial perfusion during hypertrophy, and recent studies support a significant role for TH and its endothelial cell surface integrin receptors and nuclear receptors in neovascularization during TH-induced hypertrophy. The present review examines these molecular mechanisms and intracellular signaling pathways activated in thyroid hormone-induced cardiac hypertrophy that support its therapeutic potential in the treatment of heart disease.
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PMID:Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy. 2000 76

The protein kinase C (PKC) and closely related protein kinase N (PKN) families of serine/threonine protein kinases play crucial cellular roles. Both kinases belong to the AGC subfamily of protein kinases that also include the cAMP dependent protein kinase (PKA), protein kinase B (PKB/AKT), protein kinase G (PKG) and the ribosomal protein S6 kinase (S6K). Involvement of PKC family members in heart disease has been well documented over the years, as their activity and levels are mis-regulated in several pathological heart conditions, such as ischemia, diabetic cardiomyopathy, as well as hypertrophic or dilated cardiomyopathy. This review focuses on the regulation of PKCs and PKNs in different pathological heart conditions and on the influences that PKC/PKN activation has on several physiological processes. In addition, we discuss mechanisms by which PKCs and the closely related PKNs are activated and turned-off in hearts, how they regulate cardiac specific downstream targets and pathways, and how their inhibition by small molecules is explored as new therapeutic target to treat cardiomyopathies and heart failure.
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PMID:PKC and PKN in heart disease. 3074 12