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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By means of molecular biology and genetic research the influence of genetic factors on a great variety of human diseases could be shown. In the field of cardiovascular research the genetic defects of a few monogenetic disorders, such as Marfan's syndrome and hypertrophic cardiomyopathy, have been characterized. In addition, candidate genes for polygenetic diseases, such as arterial hypertension and atherosclerosis, have been cloned. However, the identification of a candidate gene or its mutation does not prove its influence on the phenotype or the final cause of a particular disease. Only a targeted manipulation of a defined candidate gene in a transgenic animal model helps to understand the role of the gene and its product in the whole organism. Transgenic experiments can be divided into gene-addition and gene-deletion models. In a gene-addition experiment a fusiongene is microinjected into a fertilized oocyte. The fusiongene itself consists at least of a regulatory element promoter and of a DNA sequence coding for the gene product (protein) of intended overproduction. The choice of the right promoter is important for obtaining tissue-specific gene expression. The cardiac myosin light chain-2 promoter for example leads to a ventricle-specific gene expression in cardiomyocytes from early embryogenesis through adulthood. In a gene-deletion experiment on the other hand, the target gene is selectively knocked out by homologous recombination in embryonic stem (ES) cells. The selected ES-cells are then injected into blastocysts. If the ES-cells are integrated into the germ line and transmitted to the progeny, a transgenic line is established. This review article describes planning and development of transgenic animals and discusses established transgenic animal model systems with regard to cardiovascular physiology. In addition, animal models which may provide a basis for future gene therapy will be introduced.
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PMID:[A transgenic animal model: new possibilities for cardiovascular research]. 858 70

Positron emission tomography (PET) offers the unique capability of measuring specific flow (flow per unit of mass) in man by means of a regional, tridimensional, noninvasive approach. Using PET, myocardial perfusion abnormalities secondary to microvascular disorders have been investigated in arterial hypertension (AH), dilated and hypertrophic cardiomyopathy (CM), as well as in ischemic heart disease (CAD). In AH, regional perfusion at rest is within the normal range, while the coronary reserve and flow response to increase in metabolic demand are blunted. These flow abnormalities are independent of the degree of cardiac hypertrophy and the severity of AH; appropriate anti-ipertensive therapy is able to improve the perfusion abnormalities after long term treatment, independently of the effect on myocardial hypertrophy. Both dilated and hypertrophic CM demonstrate abnormal vasodilating capability, which has been shown to be present in the subclinical form of dilated DM; the reduction of coronary reserve is not related to the presence and extent of the hemodynamic impairment in dilated CM, and involves also nonhypertropied myocardium in asymmetric hypertrophic CM. These findings indicate a primary involvement of coronary microcirculation in non advanced forms of dilated and hypertrophic CM. Finally, in patients with CAD, myocardial territories supplied by angiographically normal coronary arteries show abnormal coronary reserve and flow during pacing tachycardia, indicating that, even in absence of epicardial coronary artery obstruction, microcirculation is impaired in subjects with coronary atherosclerosis. This abnormality can smooth perfusion differences between control and jeopardized regions. Accordingly, the absence of a perfusion defect during stress might indicate the presence of either a non significant stenosis or a diffuse impairment in microcirculatory function. Nuclear perfusion imaging with conventional perfusion tracers does not allow measurements of absolute blood flow, rather it provides an estimation of perfusion inhomogeneities. Although the agreement with the angiographic documentation of coronary artery disease has been frequently considered to characterize the diagnostic reliability of these techniques, the evaluation of myocardial perfusion provides an independent tool for the functional assessment of patient with heart disease. The possibility to obtain measurements of regional myocardial blood flow, provided by positron emission tomography, helps to identify the mechanisms affecting flow regulation in the myocardium. This tool thus provides a new rationale for the application of perfusion imaging, to obtain a more precise characterization of these patients, beyond the agreement with the morphological angiographic picture.
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PMID:The role of coronary microvascular dysfunction in the genesis of cardiovascular diseases. 868 Oct 18

The aim of surgery in hypertrophic cardiomyopathy is to reduce the intraventricular obstacle, increase left ventricular compliance, correct mitral regurgitation and other associated lesions, such as coronary atherosclerosis disease or endocarditis. Several surgical techniques have been proposed; myotomy, myomectomy, mitral valve replacement and mitral valve plication. The last mentioned technique combined with myomectomy can be performed safely and may represent an alternative to mitral valve replacement in cases with enlarged and elongated mitral leaflets. We review the natural evolution of the disease and its treatment, emphasizing on the possible mechanism by which surgical treatment may ameliorate the disease.
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PMID:[Myocardiopathies. IX. Surgical treatment of hypertrophic obstructive myocardiopathy: is it an underestimated alternative?]. 874 92

We describe an unusual case of acute myocardial infarction due to vasospasm in a 13-year-old boy. He was admitted to our hospital with severe congestive heart failure and shock. He had experienced a feeling of chest oppression with dyspnea while running, which grew worse. He then lost consciousness and was brought by ambulance to our intensive care unit. He had had similar but milder episodes of chest oppression months earlier. The family history revealed that his father had died suddenly from hypertrophic cardiomyopathy and that his grandmother also had hypertrophic cardiomyopathy. On admission, the patient was bathed in a cold sweat, his pulse was weak, and his blood pressure was too low to measure. Coarse crackling and wheezing were audible in both lung fields. Administration of catecholamine and intra-aortic balloon pumping failed to stabilize the hemodynamic variables, but percutaneous cardiopulmonary support proved to be lifesaving. Coronary arteriography performed during his convalescence showed on evidence of atherosclerosis. The acetylcholine provocation test ultimately revealed a diagnosis of acute myocardial infarction due to vasospasm.
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PMID:Acute myocardial infarction due to vasospasm in a 13-year-old-boy. 922 1

Atherosclerosis and its vascular sequela are responsible for considerable morbidity and mortality rates. Several risk factors have been implicated in the pathogenesis of atherosclerosis, and the search for other risk factors continues on the medical horizon. Renin-angiotensin system (RAS), a multienzyme, multilocale axis, has been extensively studied as an important mediator of atherosclerosis. Recently, the tissue-based angiotensin system has been suggested as the most significant pathway of RAS. A genetic polymorphism in the human gene for the angiotensin-converting enzyme (ACE), one of the two enzymes of RAS, has been found to have a strong association with higher risk for acute coronary events, sudden cardiac death, vascular restenosis after angioplasty, and idiopathic and hypertrophic cardiomyopathy. Clinical and animal data support angiotensin II to be the final common pathway in the enzyme cascade of RAS and ACE as the key enzyme in the generation of Angiotensin II. ACE gene polymorphism appears to modify expression of cellular and free ACE levels and could represent a genetic marker for cardiovascular disease.
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PMID:Renin-angiotensin system: genes to bedside. 973 52

This review introduces recent progress in molecular genetics of cardiovascular diseases. Many genes and their mutations causing familial cardiovascular diseases have been discovered, including familial hypertrophic cardiomyopathy which is caused by mutated cardiac beta myosin heavy chain, light chains, troponin T, troponin I, or alpha-tropomyosin, and long QT syndrome by KvLQT1, HERG, minK or cardiac voltage-dependent Na channel mutation. The mutations in causative genes can affect clinical courses of diseases; amino acid substitutions of cardiac beta myosin heavy chain with charge changes seem to cause poorer prognosis of hypertrophic cardiomyopathy. Besides monogenic diseases, there are many cardiovascular diseases affected with genetic polymorphisms, such as hypertension, ischemic heart disease and atherosclerosis. Specific amino acid mutations or polymorphisms in the promoter region of the genes are known to become a risk factor of these diseases. Polymorphisms of genes encoding apolipoprotein E, angiotensin converting enzyme, angiotensinogen and endothelial NO synthase (ecNOS) have been well characterized as an important risk factor of cardiovascular diseases. We recently found a novel gene which seems to affect human aging phenotype and vascular endothelial function. It is important as a future study to clarify the regulatory mechanisms of the klotho gene in the cardiovascular system and the clinical significance of klotho gene polymorphisms.
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PMID:[Molecular genetics of cardiovascular diseases]. 956 64

We have long known that there are diseases which are inherited from the parents, but it has not been until this last decade, with the introduction of the techniques of molecular biology, that we have been able to study them. These techniques have enable us to localize and detect the gene that causes a disease in the members of a family. The identification of a disease-causing gene does not lead only to the diagnosis and possible treatment of a very select patient population (the one with the familial disease), but also to a better understanding of the molecular basis and pathogenesis of the non-familial forms of the disease. Cardiology, despite having received these techniques more slowly, is now completely. Involved in the study of the molecular basis of cardiac diseases. The first gene to be mapped was that of hypertrophic cardiomyopathy in 1989. Since then, advances have been achieved at all levels in familial cardiac diseases. Hypertension, atherosclerosis, congenital heart diseases, and arrhythmias have all benefitted from the new techniques. Spectacular progress has been achieved in understanding familial heart rhythm disturbances, like long QT syndrome, both as congenital and acquired diseases. In the last five years 4 loci and 3 genes have been identified. The first studies of genetic based therapy have shown that in the near future patients with receive medication depending on the affected gene. Other familial arrhythmias are presently under study. Loci have been detected in some, such as bundle branch block and familial atrial fibrillation. At the speed that the techniques are evolving, and with the impressive advances of the Human Genome Project, we can expect to find the rest of the genes causing familial diseases in the next few years. These results are encouraging and clearly indicate the need for genetic diagnosis in all patients with these diseases. The diagnostic and therapeutic implications of all these discoveries could be of paramount importance.
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PMID:[Genetic bases of arrhythmias]. 960 99

The retrospective analysis of 1500 forensic autopsies after sudden cardiac death showed that 80 (77 men, three women) had died following sport, for which they had been inadequately trained. The chosen sport (both dynamic and static), and the cardiac pathology discovered during autopsy make it possible to divide the population into two groups. Group 1 were those under 30 years of age (27 cases) engaged in jogging, gymnastics, rugby, tennis and boxing who suffered from hypertrophic cardiomyopathy (29.6%), arrhythmogenic right ventricular cardiomyopathy (25.9%), non-atherosclerotic (14. 8%), aortic stenosis (7.4%), atrial septal defect (3.7%), stenosing coronary atherosclerosis (3.7%), and structural abnormalities of the His bundle (3.7%). Group 2 were those over 30 years of age (53 cases), engaged in swimming, cycling, jogging and football. The cardiac lesions responsible were stenosing atherosclerotic coronary disease (49%), non-atherosclerotic coronary disease (1.8%), hypertrophic cardiomyopathy (20%), obstructive cardiomyopathy (4.8%), structural abnormalities of the His bundle (7.4%), myocardic bruise scar (4%), and arrhythmogenic right ventricular cardiomyopathy (3. 7%). In both groups, dilated cardiomyopathy occurred with identical frequency (11%).Conclusions The lesions discovered are the same as those identified in professional athletes, when the body tries to avoid mortal rhythmic decompensation in the case of an over-loading volume and tension during an ill-adapted effort. Forensic autopsy should establish these anomalies because the transmissible genetic characteristics of some of them could underline the need for check-ups in other members of the family.
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PMID:Undetected cardiac lesions cause unexpected sudden cardiac death during occasional sport activity. A report of 80 cases. 1032 96

From 1978 to 1993 in the Veneto region, we collected 200 cases of sudden death in the young (</=35 years). Sudden death was cerebral in 15 cases (7.5%), respiratory in 10 (5%), and cardiovascular in 163 (81.5%), whereas it remained unexplained in 12 cases (6%). Among cardiovascular sudden death, obstructive coronary atherosclerosis accounted for 23% of cases, arrhythmogenic right ventricular cardiomyopathy for 12.5%, mitral valve prolapse for 10%, conduction system abnormalities for 10%, congenital coronary artery anomalies for 8.5%, myocarditis for 7.5%, hypertrophic cardiomyopathy for 5.5%, aortic rupture for 5.5%, dilated cardiomyopathy for 5%, nonatherosclerotic-acquired coronary artery disease for 3.5%, postoperative congenital heart disease for 3%, aortic stenosis for 2%, pulmonary embolism for 2%, and other causes for 2%. Cardiac arrest remained unexplained in 6% of the cases. Specific pathology and pathogenetic mechanisms of each disease were investigated and correlated with clinical signs and symptoms in detail. A large spectrum of cardiovascular disorders, both congenital and acquired, may represent the organic substrate of sudden death in the young. The underlying abnormality is frequently concealed and discovered only at postmortem examination. Most of the diseases, although asymptomatic, are potentially detectable during life with proper imaging tests.
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PMID:Cardiovascular causes of sudden death in young individuals including athletes. 1042 63

Cardiovascular diseases are the most important cause of death and hospitalisation in industrialised countries. Although pharmacological, interventional and surgical therapy has achieved major progress during the past 25 years, most therapeutic measures are only transiently effective or require life-long medication. Molecular cardiology aims at applying molecular biological methods for both diagnosis and treatment of cardiovascular disease. With respect to diagnosis of cardiac diseases such as hypertrophic cardiomyopathy or the long QT syndrome, it has become possible to characterise mutations in the genome responsible for the disease process. It is interesting that different mutations inducing hypertrophic cardiomyopathy are associated with a different prognosis and survival time. This example demonstrates that molecular biological analysis allows a better estimation of the individual risk in patients with a monogenetic disease. Such diseases are an important target for genetic therapies, as transfection of normal copies of the diseased gene would potentially cure the patient. Clinical experience has so far only been obtained in patients with familial hypercholesterolaemia and mutations in the LDL receptor. Molecular biology also permits a better understanding of the pathogenesis of atherosclerosis, which is responsible for most cardiovascular disease. Atherosclerosis is a disease of conduit arteries such as the aorta and the coronary arteries. In recent years it has become possible to characterise better the molecular and cellular changes leading to endothelial dysfunction, coronary vasospasm, adhesion of monocytes and lymphocytes, proliferation and migration of vascular smooth muscle cells, and formation of extracellular matrix. This improved understanding has led to new therapeutic approaches, although a genetic intervention is not probable for the moment due to the complexity of the disease process. Balloon dilatation of coronary arteries has generated a new disease, namely restenosis. Vascular remodelling and proliferation are of major importance for this disease. Many cellular mechanisms have been characterised, and gene therapeutic strategies including signal transduction and cell cycle regulation have already been investigated experimentally. Coronary bypass graft disease represents another target for gene therapy in the vascular system. Many experimental and a few clinical protocols have been performed with the saphenous vein. Yet another strategy for gene therapy is the endogenous formation of new vessels due to the effect of vascular endothelial growth factor. Molecular cardiology is a new and promising approach to a better understanding of cardiovascular disease. Genetic analysis is already established for the diagnosis of single gene disorders and, in addition, allows a more precise prognostic evaluation. Cardiovascular gene therapy has been focussing mainly on angiogenesis; other strategies, however, are under investigation mainly in an experimental setting.
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PMID:[Gene therapy in heart diseases]. 1060 53


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