Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using saponin skinned fibers, we investigated whether decreased myofilament calcium responsiveness and contractile activation may in part contribute to heart failure in an animal model of idiopathic spontaneous cardiomyopathy (SCM). We addressed the question as to whether there are adaptive changes at the level of the thin myofilaments in turkey poults with SCM. The calcium concentration ([Ca2+]) required for 50% activation ([Ca2+]50%) was 0.80 +/- 0.12 microM (n = 12) vs. 0.76 +/- 0.08 microM (n = 12) and the Hill coefficient was 1.98 +/- 0.20 (n = 12) vs. 2.14 +/- 0.38 (n = 12) for control and SCM muscles respectively. Maximal Ca(2+)-activated force was not different between control fibers and fibers from failing hearts (3.83 +/- 0.88 g/mm2 vs. 3.65 +/- 0.39 g/mm2). These data indicate there are no differences in calcium-activation between fibers from control and failing myocardium. The effects of caffeine, an agent that increases myofilament Ca2+ sensitivity, were also studied. Addition of 10 mM caffeine resulted in a 0.06 pCa unit leftward shift of the force-pCa relationship in control hearts and 0.14 pCa units in SCM hearts. Caffeine (30 mM) increased force by 26 +/- 2.1% (n = 7) in control fibers and 44.5 +/- 8.7% (n = 8) in myopathic fibers at a pCa of 6.0. The increased responsiveness of muscles from failing hearts to caffeine indicates adaptive changes at the level of the thin myofilaments. Addition of dibutyryl-3',5'-cyclic-Adenosine Monophosphate (D-cAMP) resulted in a 0.21 pCa rightward shift on the calcium axis to higher intracellular calcium concentrations in control myocardium and 0.38 pCa units in SCM failing myocardium. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. In this analysis the frequency at which dynamic stiffness is minimum is taken as a measure of cross-bridge cycling rate. In control muscles, the frequency of minimum stiffness (fmin) was 1.20 +/- 0.11 (n = 4) whereas it was 0.71 +/- 0.08 Hz (n = 4) in myopathic muscles. The addition of 10 microM D-cAMP shifted fmin from 1.20 +/- 0.11 Hz to 1.68 +/- 0.09 Hz (delta = 0.48 +/- 0.06) in control fibers whereas in SCM fibers it caused greater shift of fmin from 0.71 +/- 0.08 Hz to 1.73 +/- 0.08 Hz (delta = 1.02 +/- 0.07). This differential effect of D-cAMP indicates adaptive changes at the level of the myofilaments.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium-activated force in a turkey model of spontaneous dilated cardiomyopathy: adaptive changes in thin myofilament Ca2+ regulation with resultant implications on contractile performance. 133 13

The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrhythmic phenotypes in carrier patients. In addition, acquired malfunctions of Na(V)1.5 that are secondary to cardiac disorders such as heart failure and cardiomyopathies, may also play significant roles in arrhythmogenesis. While it is clear that the regulation of Na(V)1.5 protein expression and function tightly depends on genetic mechanisms, recent studies have demonstrated that Na(V)1.5 is the target of various post-translational modifications that are pivotal not only in physiological conditions, but also in disease. In this review, we examine the recent literature demonstrating glycosylation, phosphorylation by Protein Kinases A and C, Ca(2+)/Calmodulin-dependent protein Kinase II, Phosphatidylinositol 3-Kinase, Serum- and Glucocorticoid-inducible Kinases, Fyn and Adenosine Monophosphate-activated Protein Kinase, methylation, acetylation, redox modifications, and ubiquitylation of Na(V)1.5. Modern and sensitive mass spectrometry approaches, applied directly to channel proteins that were purified from native cardiac tissues, have enabled the determination of the precise location of post-translational modification sites, thus providing essential information for understanding the mechanistic details of these regulations. The current challenge is first, to understand the roles of these modifications on the expression and the function of Na(V)1.5, and second, to further identify other chemical modifications. It is postulated that the diversity of phenotypes observed with Na(V)1.5-dependent disorders may partially arise from the complex post-translational modifications of channel protein components.
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PMID:Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications. 2574 40

Macrovascular complications of diabetes like cardiovascular diseases appear to be one of the leading causes of mortality. Current therapies aimed at counteracting the adverse effects of diabetes on cardiovascular system are found to be inadequate. Hence, there is a growing need in search of novel targets. Adenosine Monophosphate Activated Protein Kinase (AMPK) is one such promising target, as a plethora of evidences pointing to its cardioprotective role in pathological milieu like cardiac hypertrophy, atherosclerosis and heart failure. AMPK is a serine-threonine kinase, which gets activated in response to a cellular depriving energy status. It orchestrates cellular metabolic response to energy demand and is, therefore, often referred to as "metabolic master switch" of the cell. In this review, we provide an overview of patho-mechanisms of diabetic cardiovascular disease; highlighting the role of AMPK in the regulation of this condition, followed by a description of extrinsic modulators of AMPK as potential therapeutic tools.
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PMID:Role of AMPK in Diabetic Cardiovascular Complications: An Overview. 2973 67