Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerotic vascular disease becomes a clinical problem when there is sufficient atherosclerotic plaque burden and/or endothelial dysfunction to cause a limitation of nutrient blood flow to tissues. However, once myocardial infarction has occurred, there is little, if any, way to stimulate the growth of new blood vessels or cardiac muscle to replace that which has been lost. The potential use of hematopoietic stem cells (HSCs) to treat cardiovascular disease has recently been suggested from preclinical and clinical studies. HSCs are precursors of all the blood cells, but they may also give rise to cells of the vascular system, endothelial cells in the form of endothelial progenitor cells (EPCs). Clinical trials have been conducted in patients with either acute myocardial infarction or limb ischemia to determine the initial effectiveness and safety of this treatment approach. These studies demonstrated the potential clinical effectiveness of this stem cell approach to the treatment of patients with acute myocardial ischemia and limb ischemia. Today, more preclinical studies are planned to elucidate the mechanism by which transplanted stem cells can home and differentiate into these endothelial cells and cardiac muscle cells. At the same time, new clinical trials are planned to evaluate both chronic, stable as well as acute myocardial ischemia and limb ischemia with CD34+ and CD133+ stem cells, as well as with further selected EPCs and mesenchymal stem cells.
 ...
PMID:Cardiovascular disease: potential impact of stem cell therapy. 1503 Feb 72

The gene currently known as SLC22A5 was already sequenced in the Human Genome project, and it was annotated as the gene of the high affinity carnitine transporter (OCTN2) in 1998. After the verification of the real function of the OCTN2 several disease related mutations of the gene have been identified, albeit the entity of the primary carnitine deficiency syndrome (OMIM 212140) was separated earlier. Besides the description of the biochemical characteristics of the transporter the present review gives a summary on the mutation spectrum and the developing phenotypes according to the literature available on the Medline and to own observations. The disease spectrum includes the involvement of the cardiac muscle and the liver primarily, however, a relatively wide phenotype variability has been observed even with the same mutations. Metabolic crisis or cardiac arrest can develop in homozygotes. Since the carnitine plays a regulatory role in the mitochondrial oxidation of the long chain fatty acids, loss of OCTN2 function lead to severe impairment of the intracellular metabolism at biochemical level, which can explain the development of a severe, even life threatening condition. The cardiac symptoms can be well influenced by carnitine administration. There are indications that cardiac manifestations can develop even in heterozygotes probably in association with the gene-dose relationship; in the laboratory of the author a heterozygous C-->T transition at the 15 np of the exon V of the OCTN2 in a patient with mild cardiomyopathy and ischemic heart disease was verified. This results in a serine 280 phenylalanine (S280F) exchange affecting thereby one of the putative protein C kinase dependent phosphorylation sites.
 ...
PMID:[The human OCTN2 carnitine transporter and its mutations]. 1512 18

The contribution that mitochondria make to cardiac function extends well beyond their critical bioenergetic role as a supplier of ATP. The organelle plays an integral part in the regulatory and signaling events that occur in response to physiological stresses, including but not limited to myocardial ischemia and reperfusion, hypoxia, oxidative stress, and hormonal and cytokine stimuli. Research on both intact cardiac muscle tissue and cultured cardiomyocytes has just begun to probe the nature and the extent of mitochondrial involvement in interorganelle communication, hypertropic growth, and cell death. This review covers particular aspects of the newly emerging field of mitochondrial medicine offering a critical guide in the assessment of mitochondrial participation at the molecular and biochemical levels in the multiple and interrelated signaling pathways, gauging the effect that mitochondria have as a receiver, integrator, and transmitter of signals on cardiac phenotype. We also discuss future directions that may impact on the treatment of cardiac diseases.
 ...
PMID:Heart mitochondria signaling pathways: appraisal of an emerging field. 1522 Oct 79

One of the most compelling issues to impact on contemporary cardiology is arguably the phenomenon of programmed cell death or apoptosis. Studies in the nematode Caenorhabditis elegans provided the first indication that determinants of cell fate crucial for normal worm development were under genetic influences of the ced-3 and ced-9 genes, which promote or prevent cell death, respectively. Extrapolation of these seminal findings led to the discovery of the mammalian ced-3 and ced-9 homologs, which broadly encompass a family of cellular cysteine proteases known collectively as caspases and the Bcl-2 proteins. In quiescent cells, caspases exist as inactive zymogens that are readily activated by autocatalytic processes or by other caspases following a death signal. The caspase-dependent cleavage of intracellular substrates results in the biochemical dismantling of the cell and morphological features characteristic of apoptosis. Recently, a mitochondrial death pathway for apoptosis has been proposed. Perturbations to mitochondria resulting in the loss of mitochondrial membrane potential, DeltaPsim, permeability transition pore (PTP) opening and the release of pro-apoptotic factors by mitochondria including cytochrome c, second mitochondrial activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO), AIF, and others are considered terminal events in the apoptotic pathway. Bcl-2 and related family members are characterized by their ability to promote or prevent cell death. These proteins exert their pro- or anti-apoptosis function by impinging on components of the cell death pathway that underlie caspase activation, mitochondrial dysfunction or both. The limited regenerative potential of the adult cardiac muscle itself, together with the heightened and exciting possibility of regenerating cardiac muscle with cardiac progenitor cells, acknowledges the need for new strategies to suppress and/or prevent inappropriate cardiac cell death in patients with ischemic heart disease or heart failure patients as a therapeutic means of preserving cardiac pump function after injury.
 ...
PMID:Apoptosis of ventricular myocytes: a means to an end. 1562 17

This clinically oriented review presents main principles of metabolism of cardiac muscle, pathophysiology of myocardial hibernation and stunning, as well as methodological principles of positron emission tomography (PET) of the heart with (18)F-fluoro-2-deoxyglucose ((18)F-FDG). Diagnostic and prognostic value of (18)F-FDG PET and scintigraphic sings of disturbed myocardial viability, contractility and metabolism are also described. Efficacy of (18)F-FDG PET is compared with other imaging methods such as radionuclide, ultrasound and radiological. Literature data and clinical cases demonstrate importance of preoperative diagnosis of hibernating myocardium in patients with ischemic heart disease. (18)F-FDG PET is a basic method of detection of potentially reversible pathological states of the heart (hibernation and stunning); it has high sensitivity and specificity as well as predictive power in relation to forthcoming course of ischemic heart disease. This noninvasive method of investigation provides unique information on severity of ischemic heart disease for stratification of patients in risk groups and selection of candidates for coronary artery bypass surgery or cardiac transplantation.
 ...
PMID:[Positron emission tomography with (18)F-fluoro-2-deoxyglucose in cardiological diagnosis]. 1579 20

Coronary atherosclerotic disease is the leading cause of mortality in industrialized countries. The disease can remain silent for years, being diagnosed only after acute myocardial infarction in about 50% of cases. Coronary angiography is the reference standard for coronary imaging. However, it is invasive and costly, requiring intra-arterial catheterization. In addition, coronary angiography does not visualize the arterial wall, but only the lumen. A reliable non-invasive imaging technique showing changes in both the arterial wall and the lumen would be highly useful, especially for early diagnosis. Recently, multislice computed tomography (CT) was shown to be capable of visualizing not only the coronary arteries (lumen and wall), but also the cardiac muscle, with high spatial resolution. Multislice CT provides high-quality 3D images of coronary arteries. Initial results with 4, 16 and now 64-slice CT, by comparison with conventional angiography, are very promising, and multislice CT technology is advancing rapidly. Non-invasive visualization of the coronary arteries with accurate detection of stenosis is now possible in practice using ECG-gated 16-slice CT Multislice CT can also detect non stenotic coronary plaque. Finally, visualization of cardiac muscle by multislice CT makes it possible to detect myocardial ischemia.
 ...
PMID:[Non-invasive coronary artery imaging using multislice computed tomography]. 1624 84

Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC). These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI) with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD). There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens), as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear cells. The maximum number of stem cells was found early in ST-segment elevation myocardial infarction (<12 hours) with subsequent decrease through the 7-day follow-up and with concomitant changes in the levels of cytokines involved in the inflammatory response and stem cell recruitment. Moreover, peak expression of cardiac muscle and endothelial markers occurred at the same time as the most significant increase in CD34/CXCR4+ stem cell number. The SDF-1/CXCR-4 axis seems particularly important in stem/muscle progenitor cell homing, chemotaxis, engraftment and retention in ischaemic myocardium. The significance of autologous stem cells mobilization in terms of cardiac salvage and regeneration needs to be proved in humans but it seems to be a reparative mechanism triggered early in the course of acute coronary syndromes.
 ...
PMID:Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes. 1638 90

Although heart failure is a final common consequence of various heart diseases and is a leading cause of mortality worldwide, the precise molecules and signaling pathways that mediate heart failure progression are largely undefined. In this review, we discuss about the potential mechanisms of heart failure focusing on three subjects, (i) myocardial ischemia, (ii) cardiac muscle cell death, and (iii) abnormalities in calcium handling. These factors are not mutually independent but considered to contribute to the pathogenesis of contractile dysfunction and heart failure in a cooperative manner. Elucidation of molecular mechanisms of heart failure will lead to the development of novel therapeutic strategies for heart diseases.
 ...
PMID:[Molecular mechanisms of congestive heart failure]. 1668 60

Chronic diabetes precipitates ischaemic heart disease (IHD) and many other disorders. IHD inturn is shown in the form of angina initially. According to EUROPA study, the incidence of angina is high in type II diabetics. Gliclazide, a second generation sulphonylurea derivative is widely used in the treatment of type-II diabetes and is known to release insulin by K(+) channel inhibition. Nicorandil, a newer antianginal drug widely used now a days acts by opening potassium channels in the cardiac muscle cell and also by releasing nitric oxide. However its action on pancreatic cell K(+) channel is not known. Since there is possibility for drug interaction leading to decreased activity of gliclazide the present study was conducted to evaluate the effect of the combination. Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 1.8 mg/kg bd. wt. of nicorandil and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 1.4 mg/1.5 kg bd. wt. of nicorandil and their combination given orally. Blood samples were collected in rats from retro orbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h and by marginal ear vein puncture in rabbits at 0, 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 h. All the blood samples were analysed for glucose by GOD/POD method. The blood samples of rabbits were analysed by HPLC for gliclazide. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 1 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h, while nicorandil alone produced significant hyperglycaemia at 4 h and reduced the effect of gliclazide with no significant change in pharmacokinetics when administered in combination. The interaction observed appears to be pharmacodynamic at the receptor level as expected.
 ...
PMID:Influence of nicorandil on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits. 1671 84

The structure of the NH2-terminal region of troponin T (TnT) is hypervariable among the muscle type-specific isoforms and is also regulated by alternative RNA splicing. This region does not contain binding sites for other thin filament proteins, but alteration of its structure affects the Ca2+ regulation of muscle contraction. Here we report a truncated cardiac TnT produced during myocardial ischemia reperfusion. Amino acid sequencing and protein fragment reconstruction determined that it is generated by a posttranslational modification selectively removing the NH2-terminal variable region and preserving the conserved core structure of TnT. Triton X-100 extraction of cardiac muscle fibers promoted production of the NH2-terminal truncated cardiac TnT (cTnT-ND), indicating a myofibril-associated proteolytic activity. Mu-calpain is a myofibril-associated protease and is known to degrade TnT. Supporting a role of mu-calpain in producing cTnT-ND in myocardial ischemia reperfusion, calpain inhibitors decreased the level of cTnT-ND in Triton-extracted myofibrils. Mu-calpain treatment of the cardiac myofibril and troponin complex specifically reproduced cTnT-ND. In contrast, mu-calpain treatment of isolated cardiac TnT resulted in nonspecific degradation, suggesting that this structural modification is relevant to physiological structures of the myofilament. Triton X-100 treatment of transgenic mouse cardiac myofibrils overexpressing fast skeletal muscle TnT produced similar NH2-terminal truncations of the endogenous and exogenous TnT, despite different amino acid sequences at the cleavage site. With the functional consequences of removing the NH2-terminal variable region of TnT, the mu-calpain-mediated proteolytic modification of TnT may act as an acute mechanism to adjust muscle contractility under stress conditions.
 ...
PMID:Selective deletion of the NH2-terminal variable region of cardiac troponin T in ischemia reperfusion by myofibril-associated mu-calpain cleavage. 1698 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>