Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an increased incidence of heart disease in patients with chronic nephrotic syndrome (NS), which may be attributable to the malnutrition and activated inflammatory state accompanying the sustained proteinuria. In this study, we evaluated renal function, cardiac morphometry, contractile function, and myocardial gene expression in the established puromycin aminonucleoside nephrosis rat model of NS. Two weeks after aminonucleoside injection, there was massive proteinuria, decreased creatinine clearance, and a negative sodium balance. Skeletal and cardiac muscle atrophy was present and was accompanied by impaired left ventricular (LV) hemodynamic function along with decreased contractile properties of isolated LV muscle strips. The expression of selected cytokines and proteins involved in calcium handling in myocardial tissue was evaluated by real time polymerase chain reaction. This revealed that the expression of interleukin-1beta, tumor necrosis factor-alpha, and phospholamban were elevated, whereas that of cardiac sarco(endo)plasmic reticulum calcium pump protein was decreased. We suggest that protein wasting and systemic inflammatory activation during NS contribute to cardiac remodeling and dysfunction.
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PMID:Cardiac remodeling and dysfunction in nephrotic syndrome. 1745 79

Jervell, Lange-Nielsen syndrome is a condition that causes profound hearing loss and disruption of the normal cardiac rhythm. This disorder is a form of long QT syndrome, a cardiac disorder that causes the cardiac muscle to take longer than usual to recharge between beats. A retrospective case study was performed to document cochlear implantation in three profoundly deaf children (two of them siblings) with Jervell, Lange-Nielsen syndrome. We discuss diagnosis and management of this syndrome and also the long-term performance of cochlear implantation in these Iranian patients, referring especially to the role of the ENT specialist in diagnosis and treatment. The collected data show that cochlear implantation can be relatively safely performed in patients with Jervell, Lange-Nielsen syndrome and that these children received significant benefit from cochlear implantation.
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PMID:Cochlear implantation in children with Jervell, Lange-Nielsen syndrome. 1749 28

Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure that the heart can operate under steady-state conditions on a beat by beat basis. To this end we discuss the relative importance of various sources and sinks of Ca(2+) responsible for initiating contraction and relaxation in cardiac myocytes and how these can be manipulated to regulate the Ca(2+) content of the major Ca(2+) store, the sarcoplasmic reticulum (SR). We will present a simple feedback system detailing how such control can be achieved and highlight how small perturbations to the steady-state operation of the feedback loop can be both beneficial physiologically and underlie changes in systolic Ca(2+) in ageing and heart disease. In addition to manipulating the amplitude of the normal systolic Ca(2+) transient, the tight regulation of SR Ca(2+) content is also required to prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR. Such diastolic events are a major factor contributing to the genesis of cardiac arrhythmias in disease situations and in recently identified familial mutations in the SR Ca(2+) release channel (ryanodine receptor, RyR). How such diastolic release arises and potential mechanisms for controlling this will be discussed.
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PMID:Analysis of cellular calcium fluxes in cardiac muscle to understand calcium homeostasis in the heart. 1750 80

In excitable cells such as skeletal and cardiac myocytes excitation-contraction coupling is an important intermediate step between initiation of the action potential and induction of contraction. This process is predominantly controlled by Ca(2+) release from the sarcoplasmic reticulum via the ryanodine receptor. This very large protein (MW 560 kDa) exists as a homotetramer (~2.2 MDa) and is expressed in three isoforms: RyR1, expressed in skeletal muscle; RyR2, expressed in cardiac muscle; and RyR3, expressed in various cells at lower levels than the other isoforms. Release of Ca(2+) via RyR2 is induced by Ca(2+) influx through L-type Ca(2+) channels and is modulated by multiple factors, including phosphorylation of RyR2 protein by protein kinase A, calmodulin kinase II and FKBP12.6, and stimulation via the beta-adrenergic receptor signaling pathway. Hyperphosphorylation of RyR2 induces Ca(2+) leak during diastole, which can cause fatal arrhythmias and lead to heart failure. This makes RyR2 an important therapeutic target. Although there are few commercially available drugs that inhibit Ca(2+) leak from RyR2, K201 (JTV-519), a benzothiazepine derivative, has emerged as a new ryanodine receptor-selective agent that prevents atrial fibrillation, ventricular arrhythmias, heart failure and exercise-induced sudden cardiac death. In this review, we discuss recent advances in our understanding of the basic structure and function of ryanodine receptors, their involvement in heart disease, and the development of drugs to prevent ryanodine receptor malfunction and recent patents.
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PMID:Ryanodine receptor: a novel therapeutic target in heart disease. 1822 Nov 9

Heart development is a precisely coordinated process of cellular proliferation, migration, differentiation, and integrated morphogenetic interactions, and therefore it is highly susceptible to developmental anomalies such as the congenital heart disease (CHD). One of the major causes of CHD has been shown to be the mutations in key cardiac transcription factors, including nkx2.5. Here, we report the analysis of zebrafish mutant ftk that showed a progressive heart malformation in the later stages of heart morphogenesis. Our analyses revealed that the cardiac muscle maturation and heart morphogenesis in ftk mutants were impaired because of the disorganization of myofibrils. Notably, we found that the expression of nkx2.5 was down-regulated in the ftk heart despite the normal expression of gata4 and tbx5, suggesting a common mechanism for the occurrence of ftk phenotype and CHD. We identified ftk to be a loss-of-function mutation in a connexin gene, cx36.7/early cardiac connexin (ecx), expressed during early heart development. We further showed by a rescue experiment that Nkx2.5 is the downstream mediator of Ecx-mediated signaling. From these results, we propose that the cardiac connexin Ecx and its downstream signaling are crucial for establishing nkx2.5 expression, which in turn promotes unidirectional, parallel alignment of myofibrils and the subsequent proper heart morphogenesis.
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PMID:Zebrafish early cardiac connexin, Cx36.7/Ecx, regulates myofibril orientation and heart morphogenesis by establishing Nkx2.5 expression. 1833 97

One of the most exciting cell biology fields of study concerns the physiology and pathology of fat. The basic assumptions once held concerning the function of adipose tissue have been shown to be oversimplified or sometimes completely wrong. Fat does more than store excess energy; it is actually the largest endocrine organ in the body, and it may be one of the most active. Adipocytes release hormones and other molecules that act on nearby tissues and travel through the vasculature to distant sites, such as the brain, skeletal muscle, and liver. Under conditions of normal weight, those signals help the body to suppress hunger, utilize glucose, and decrease the risk of cardiovascular disease. However, under conditions of obesity, the hormones (or the proteins that bind the hormones) become abnormal and can result in states of chronic inflammation leading to diabetes and heart disease. In addition, excessive fat can lead to the accumulation of lipid droplets in nonfat cells, including skeletal and cardiac muscle. Although some lipid droplets are used as an immediate source of energy for cells, large numbers of stored droplets can cause cellular damage and cell death. The purposes of this article are to review the normal and deviant signals released by fat cells, to draw a link between those signals and chronic diseases such as diabetes, and to discuss the role of exercise in reversing some of the deviant signaling perpetrated by excess fat.
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PMID:Intricacies of fat. 1880 55

Impaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross myofibril disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is required for direct transcriptional regulation of the genes encoding the structural proteins alpha-actinin, N-RAP and zyxin, which collectively function to maintain an actin-alpha-actinin interaction as the fundamental association of the sarcomere. Aspects of abnormal heart development and the manifestation of a subset of muscular-based disease have previously been attributed to mutations in key structural proteins. Our study reveals an essential requirement for direct transcriptional regulation of sarcomere integrity, in the context of enabling foetal cardiomyocyte hypertrophy, maintenance of contractile function and progression towards inherited or acquired myopathic disease.
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PMID:Prox1 maintains muscle structure and growth in the developing heart. 1909 69

The importance of supporting energy production in heart cells and the preservation of the mitochondria in these cells will be the focus of a new frontier in cardiovascular prevention, treatment, and management. Many physicians are not trained to look at heart disease in terms of cellular biochemistry; therefore, the challenge in any metabolic cardiology discussion is in taking the conversation from the "bench to the bedside." An understanding of the vital role that adenosine triphosphate (ATP) plays in the heart is critical for any physician or clinician considering therapeutic options that support ATP production and turnover in jeopardized cardiac muscle cells. Metabolic therapies that help cardiomyocytes meet their absolute need for ATP fulfill a major clinical challenge of preserving pulsatile cardiac function while maintaining cell and tissue viability. D-ribose, L-carnitine, and coenzyme Q10 work in synergy to help the ischemic or hypoxic heart preserve its energy charge. This article introduces how ATP, diastolic heart function, and metabolic support help maintain cardiac energy by preserving ATP substrates. Part 2 will investigate an in-depth biochemical discussion of congestive heart failure with physiologic, pathophysiologic, and treatment considerations.
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PMID:Metabolic cardiology: the missing link in cardiovascular disease. 1928 82

The hormonal derivative of vitamin D, 1,25-dihydroxyvitamin D (1,25[OH](2)D) or calcitriol, has been implicated in many physiologic processes beyond calcium and phosphorus homeostasis, and likely plays a role in several chronic disease states, in particular, cardiovascular disease. Experimental data suggest that 1,25(OH)(2)D affects cardiac muscle directly, controls parathyroid hormone secretion, regulates the renin-angiotensin-aldosterone system, and modulates the immune system. Because of these biologic effects, vitamin D deficiency has been associated with hypertension, several types of vascular diseases, and heart failure. We conducted a MEDLINE search of the English-language literature (1950-2008) to identify studies that examined these relationships; additional citations were obtained from the articles retrieved from the literature search. Treatment with vitamin D lowered blood pressure in patients with hypertension and modified the cytokine profile in patients with heart failure. Measurement of serum 25-hydroxyvitamin D concentration usually provides the best assessment of an individual's vitamin D status. Serum levels below 20 ng/ml represent vitamin D deficiency, and levels above 30 ng/ml are considered optimal. Although the observational data linking vitamin D status to cardiovascular disease appear robust, vitamin D supplementation is not recommended as routine treatment for heart disease until definitive prospective, randomized trials can be carried out to assess its effects. However, such supplementation is often appropriate for other reasons and may be beneficial to cardiovascular health in certain patients.
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PMID:Vitamin D and cardiovascular disease. 1947 21

Heart muscle contraction is regulated by Ca(2+) binding to the thin filament protein troponin C. In cardiovascular disease, the myofilament response to Ca(2+) is often altered. Compounds that rectify this perturbation are of considerable interest as therapeutics. Plant flavonoids have been found to provide protection against a variety of human illnesses such as cancer, infection, and heart disease. (-)-Epigallocatechin gallate (EGCg), the prevalent flavonoid in green tea, modulates force generation in isolated guinea pig hearts (Hotta, Y., Huang, L., Muto, T., Yajima, M., Miyazeki, K., Ishikawa, N., Fukuzawa, Y., Wakida, Y., Tushima, H., Ando, H., and Nonogaki, T. (2006) Eur. J. Pharmacol. 552, 123-130) and in skinned cardiac muscle fibers (Liou, Y. M., Kuo, S. C., and Hsieh, S. R. (2008) Pflugers Arch. 456, 787-800; and Tadano, N., Yumoto, F., Tanokura, M., Ohtsuki, I., and Morimoto, S. (2005) Biophys. J. 88, 314a). In this study we describe the solution structure of the Ca(2+)-saturated C-terminal domain of troponin C in complex with EGCg. Moreover, we show that EGCg forms a ternary complex with the C-terminal domain of troponin C and the anchoring region of troponin I. The structural evidence indicates that the binding site of EGCg on the C-terminal domain of troponin C is in the hydrophobic pocket in the absence of troponin I, akin to EMD 57033. Based on chemical shift mapping, the binding of EGCg to the C-terminal domain of troponin C in the presence of troponin I may be to a new site formed by the troponin C.troponin I complex. This interaction of EGCg with the C-terminal domain of troponin C.troponin I complex has not been shown with other cardiotonic molecules and illustrates the potential mechanism by which EGCg modulates heart contraction.
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PMID:Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate. 1954 63


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