Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constant vasodilatation, inhibition of platelet and leukocyte adhesion, and local thrombolysis are the mechanisms through which an intact endothelial layer exerts its protective action on coronary circulation. A loss in these features is not only the first step in the development of atherosclerosis, but also a potent trigger for complications after revascularisation procedures. Percutaneous coronary interventions, particularly in the course of stenting, induce endothelial injury that can last up to months after the procedure. On the other hand, the preservation of endothelial function appears the best feature of arterial versus venous grafts after coronary bypass surgery. An early diagnosis either by invasive or non-invasive techniques has important implications for prognosis, and endothelial dysfunction can be effectively counteracted by medical treatment (ACE inhibitors, statins). Activated circulating platelets are present in the course of coronary artery disease, increasing the risk of thrombotic occlusion and/or plaque regrowth, after both percutaneous and surgical revascularisation. New antiplatelet agents are under development to reduce endothelium-platelet interaction. On the basis of the latest studies, coronary revascularisation should be integrated in a more complete treatment, which would take into account the complex processes involving the underlying atherosclerotic plaque.
 ...
PMID:Pathophysiology of vascular endothelium and circulating platelets: implications for coronary revascularisation and treatment. 1146 51

National and international recommendations on the management of arterial hypertension and hypercholesterolemia suggest a treatment decision based on the evaluation of absolute cardiovascular risk. In order to evaluate the cardiovascular risk level, Anderson's equation (Framingham) has been proposed but does not apply to the French population. In medical practice, cardiovascular risk has to be appreciated according to the estimated cardiovascular risk of the country or area. The limits of a decision based on cardiovascular risk have been emphasized, particularly the balance age/life expectancy in respect of early prevention of atherosclerosis. However, the benefit of treatment of hypertension with beta-blockers, diuretics and recently ACE inhibitors and calcium antagonists or hypercholesterolemia with statins has been clearly stated--the higher the cardiovascular risk the higher the benefit. Secondary prevention in patients with major cardiovascular events is effective and necessary. The discussion concerns only primary prevention and from an economic point of view may concern patients at high cardiovascular risk. The general population have to be informed on cardiovascular risk factors, and patient education must be encouraged and developed via the healthcare network.
 ...
PMID:[Prevention in cardiovascular pathology]. 1147 62

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.
 ...
PMID:ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans. 1149 59

We analyzed vascular responses (endothelial function, oxidant stress) to postprandial hypertriglyceridemia (PHTG) in patients with coronary artery disease (CAD) to reveal potential therapeutical effects of angiotensin converting enzyme inhibition (ACE-I) and of lipid lowering (fibrate). The study population (n=39, mean age: 60 years) consisted of four groups, all of which had angiographically documented CAD. A high fat group (n=9) consumed a high fat meal, a low fat group (n=9) a low fat meal, and ACE-I (n=10) or fibrate (n=11) groups consumed a high fat meal plus lisinopril or fenofibrate. Serum triglycerides (TG) increased significantly 2 h after eating a test meal in all groups with the exception of the low fat group. In the high and low fat groups changes of serum TG were positively correlated (r=0.664, P<0.005) with changes of phorbol ester-activated leukocyte superoxide anion radical (O(2-.)) formation and were negatively correlated (r=-0.488, P<0.05) with flow-mediated brachial artery dilation (FMD). There was a negative correlation (r=-0.419, P=0.094) between FMD and changes of O(2-.) formation in the high and low fat groups. In the ACE-I and fibrate groups, O(2-.) formation decreased 2 h after eating a test meal (from 5.34+/-1.01 to 3.81+/-1.15 nmol/10(6)cells per min, P<0.01, and from 4.66+/-0.91 to 4.26+/-0.97 nmol/10(6)cells per min, P=0.374, respectively). However, endothelial function did not show any significant changes 2 h after eating a test meal in all groups. PHTG increases oxidant stress and further deteriorates endothelial function, even in patients with CAD. Both ACE-I and fibrates have an antioxidant effect but no acute beneficial effects in terms of endothelial function under conditions of PHTG in CAD patients.
Atherosclerosis 2001 Sep
PMID:Impact of postprandial hypertriglyceridemia on vascular responses in patients with coronary artery disease: effects of ACE inhibitors and fibrates. 1150 Jan 88

In this investigation associations of gene complexes consisting of seven candidate for coronary atherosclerosis (ACE, AGT, NOS3, APOA1, MTHFR, PLAT, F13) with risk factors for CAD (lipid levels, blood pressure, body mass index (BMI)) were studied in Russian population. 94 male patients with CAD proven by angiography and 131 healthy individuals were involved in the case-control study. We observed a significant contribution of gene combinations ("ensembles"). ACE-MTHFR, ACE-F13, ACE-AGT-MTHFR in the variability of the total cholesterol and LDL-cholesterol levels. The "Ensembles" ACE-AGT-MTHFR were associated with variability of three atherogenic risk factors (LDL, BMI, cholesterol total). Two-locus gametic disequilibrium was analysed between gene polymorphisms. NOS3 and ACE, NOS3 and APOA1 were in gametic disequilibrium in the control group. Polymorphic markers of ACE and F13, NOS3 and F13, ACE and PLAT loci were in gametic disequilibrium in the patients. Both approaches (association analysis and gametic disequilibrium) revealed the same gene combinations contributing to the CAD risk factors. NOS3 and APOA1 markers were in gametic disequilibrium in the patients and both of them were associated with LDL. F13 and AGT were associated with systolic and diastolic blood pressure and two-locus gametic disequilibrium between F13 and AGT polymorphisms observed in the patients.
 ...
PMID:The estimation of gametic disequilibrium between DNA markers in candidate genes for coronary artery disease (CAD) and the associations of gene complexes with risk factors for CAD. 1150 73

Plasminogen activator inhibitor type-1 (PAI-1) is known to contribute to thrombus formation and to the development and the clinical course of acute and chronic cardiovascular disease, as well as of other arterial and venous thromboembolic diseases. Recently, an important role of elevated pretreatment levels of PAI-1 for failure of thrombolytic therapy of acute myocardial infarction has been discussed. PAI-1 plasma levels depend on the one hand on gene regulation but are related on the other hand to known risk factors of atherosclerosis like insulin resistance, diabetes or hypertriglyceridemia, respectively. Furthermore, an activated renin-angiotensin-aldosterone system (RAAS) significantly contributes to the upregulation of PAI-1 concentration via a receptor-mediated mechanism. In accordance to the known mechanisms of regulation of PAI-1 plasma levels, the use of specific agents like antidiabetic drugs, fibrates, statins, ACE inhibitors and angiotensin II type-1 receptor-blockers may contribute to the downregulation of circulating PAI-1 and, therefore, increase the fibrinolytic capacity and consecutively counteract the thrombotic tendency. To further improve the efficacy of thrombolytic therapy, a PAI-1 resistant variant of t-PA, TNK-t-PA, has been developed and is now available for acute myocardial infarction.
 ...
PMID:Plasminogen activator inhibitor type-1 in cardiovascular disease. Status report 2001. 1156 64

The cardiovascular system is regulated by hemodynamic and neurohumoral mechanisms. These regulatory systems play a key role in modulating cardiac function, vascular tone, and structure. Although neurohumoral systems are essential in vascular homeostasis, they become maladaptive in disease states such as hypertension, coronary disease, and heart failure. The clinical success of ACE inhibitors has led to efforts to block other humoral systems. Neutral endopeptidase (NEP) is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site. NEP is the major enzymatic pathway for degradation of natriuretic peptides, a secondary enzymatic pathway for degradation of kinins, and adrenomedullin. The natriuretic peptides can be viewed as endogenous inhibitors of the renin angiotensin system. Inhibition of NEP increases levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) of myocardial cell origin, and C-type natriuretic peptide (CNP) of endothelial cell origin as well as bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide and kinin systems, vasopeptidase inhibitors reduce vasoconstriction, enhance vasodilation, improve sodium/water balance, and, in turn, decrease peripheral vascular resistance and blood pressure and improve local blood flow. Within the blood vessel wall, this leads to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and increased local levels of bradykinin (and, in turn, nitric oxide) and natriuretic peptides. Preliminary clinical experiences with vasopeptidase inhibitors are encouraging. Thus, the combined inhibition of ACE and neutral endopeptidase is a new and promising approach to treat patients with hypertension, atherosclerosis, or heart failure.
 ...
PMID:Vasopeptidase inhibitors: a new therapeutic concept in cardiovascular disease? 1159 26

Several different techniques of low-density lipoprotein (LDL) apheresis are available for management of severe hypercholesterolemia. Among them, the adsorption system with a dextran-sulfate cellulose (DSC) column is most widely used. In addition to adsorption of LDL, DSC adsorbs plasma constituents that have the following characteristics: proteins containing apolipoprotein B (Lp[a]); proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high-molecular-weight kininogen and prekallikrein); factors with lipophilic characteristics (coagulation factor VII, coagulation factor VIII, and vitamin E); and proteins with adhesive or other characteristics (von Willebrand factor, fibronectin, serum amyloid P component, hepatocyte growth factor). The adsorption of these proteins seems to ameliorate prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of inexorable diseases, such as amyloidosis. On the other hand, the DSC column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain the functional improvement in the circulatory system, as well as hypotension during LDL apheresis, which is observed in patients taking ACE inhibitors.
 ...
PMID:Low-density lipoprotein apheresis and changes in plasma components. 1172 6

It is well-known that patients with terminal renal insufficiency are at increased risk for a future cardiovascular event. A relevant relationship also appears to apply to the early stages of renal insufficiency. The HOPE study has shown that the incidence of myocardial infarction, apoplexy and cardiovascular mortality in patients with incipient renal insufficiency is significantly raised. The study also found that the incidence of cardiovascular events is in direct proportion to the level of serum creatinine. Against this background, patients at risk can be readily identified. The HOPE study documents a considerable cardiovascular risk for patients with incipient renal insufficiency and concomitant uncomplicated hypertension, atherosclerosis or diabetes. In view of this, the use of ACE inhibitors in patients with moderate renal insufficiency should now be introduced. In the HOPE subjects, ramipril was found not only to lower the cardiovascular risk, but also to improve renal insufficiency.
 ...
PMID:[Renal failure and cardiovascular risk. Increased borderline serum creatinine--a warning sign?]. 1177 Mar 72

The circulating renin-angiotensin system plays an important role in cardiovascular homeostasis. More importantly, the local tissue renin angiotensin plays a pivotal role in cell growth and remodelling of cardiomyocytes and on the peripheral arterial vasculature. In addition, the renin angiotensin system is related to apoptosis, control of baroreflex and autonomic responses, vascular remodelling and regulation of coagulation, inflammation and oxidation. The cardioprotective and vascular protective effects of the angiotensin receptive blockade appears to be related to selective blockade of the angiotensin II (A-II) Type I (AT(1)) receptors. However, there is now growing evidence showing that some of the effects of AT-II receptor blockers (ARBs) are related to the activation of the kinin pathways. This paper will review some of the recent mechanisms related to the cardiovascular effects of angiotensin and more specifically of ARBs. This paper will present the novel data on the role of ARB in the development of atherosclerosis, vascular remodelling, coagulation balance and autonomic regulation. Finally, the role of ARBs, used alone or in combination with ACE inhibitor in patients with heart failure, will be discussed.
 ...
PMID:Therapeutic potential of angiotensin II receptor antagonists. 1177 78


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