Current medicinal chemistry. Cardiovascular and hematological agents最新文献

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Homocysteine-lowering treatment in coronary heart disease. 降低同型半胱氨酸治疗冠心病。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-10-01 DOI: 10.2174/156801605774322319
M Cesari, G P Rossi, A C Pessina
{"title":"Homocysteine-lowering treatment in coronary heart disease.","authors":"M Cesari,&nbsp;G P Rossi,&nbsp;A C Pessina","doi":"10.2174/156801605774322319","DOIUrl":"https://doi.org/10.2174/156801605774322319","url":null,"abstract":"<p><p>Homocysteine (Hcy) is a sulphur-containing amino acid product of methionine's metabolism. Hyperhomocysteinemia (HHcy) is considered an independent risk factor for cardiovascular (CV) disease, at least in high-risk patients. In fact, evidence indicates that although mild HHcy may be regarded as a minor risk factor for CHD in low-risk patients, it can play a role in triggering new events in patients with known CHD, also by interacting with the \"classical\" CV risk factors. This is of much interest because HHcy represents a correctable risk factor, inasmuch vitamin supplementation as has been shown to effectively lower total homocysteine plasma levels (tHcy). While case-control and cross-sectional studies have consistently demonstrated an association of HHcy with CV disease, prospective studies have given conflicting results. Moreover, the effect of the homocysteine-lowering treatment in preventing CV events is still under debate. Thus, it remains unclear which patients should be screened for HHcy and which ones should be treated to lower tHcy. In this paper we shall report and discuss knowledge on the potential role of HHcy in the development of CHD and on the benefits due to tHcy-lowering treatment with vitamins.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 4","pages":"289-95"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801605774322319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25659455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Aspirin and clopidogrel: a sweeping combination in cardiology. 阿斯匹林和氯吡格雷:心脏病学上的广泛组合。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368188
Antonis S Manolis, Stylianos Tzeis, George Andrikopoulos, Spyros Koulouris, Helen Melita
{"title":"Aspirin and clopidogrel: a sweeping combination in cardiology.","authors":"Antonis S Manolis,&nbsp;Stylianos Tzeis,&nbsp;George Andrikopoulos,&nbsp;Spyros Koulouris,&nbsp;Helen Melita","doi":"10.2174/1568016054368188","DOIUrl":"https://doi.org/10.2174/1568016054368188","url":null,"abstract":"<p><p>Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician's armamentarium. Clopidogrel is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A(2), which is a prothrombotic and vasoconstrictive substance. Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due to a more favorable safety profile, irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y(12) receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Both these antiplatelet agents have a potent protective effect against adverse vascular events, but the combination of these two agents has an even stronger antiplatelet effect translating into superior antithrombotic protection in coronary, cerebral or peripheral arterial disease, without an inordinate increase in bleeding complications. A number of seminal clinical trials have demonstrated and confirmed the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone, with multiple other important large-scale clinical trials currently ongoing. Newer data are being accumulated from studies where indications for the use of clopidogrel and aspirin continue to expand into other patient groups, rendering this dual antiplatelet drug therapy a sweeping combination in Cardiology. However, important issues remain to be further and more thoroughly explored about the benefit of this antiplatelet drug combination in these other patient groups, such as in patients with heart failure, where preliminary data indicate a favorable effect on thrombotic vascular events, in patients with atrial fibrillation, where there is hope that this combination may replace or be an alternative treatment modality to coumadin in certain subpopulations, in patients undergoing demanding catheter ablation procedures, where data point to a protective effect from thromboembolic events. Another pertaining issue to be further investigated is the occurrence of drug-resistance observed in some patients for both t","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"203-19"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 32
Cardiac adrenomedullin: its role in cardiac hypertrophy and heart failure. 心脏肾上腺髓质素:在心脏肥厚和心力衰竭中的作用。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368241
Toshio Nishikimi, Hiroaki Matsuoka
{"title":"Cardiac adrenomedullin: its role in cardiac hypertrophy and heart failure.","authors":"Toshio Nishikimi,&nbsp;Hiroaki Matsuoka","doi":"10.2174/1568016054368241","DOIUrl":"https://doi.org/10.2174/1568016054368241","url":null,"abstract":"<p><p>Co-localization of adrenomedullin (AM) and its receptor components such as calcitonin receptor like receptor (CRLR), receptor activity modifying protein (RAMP)2 and RAMP3 in peripheral tissues, including the heart, kidney, and vasculature, suggests an important role for the peptide as a regulator of cardiovascular function. Indeed, we previously reported that AM gene expression and / or immunoreactivity are increased in the ventricles of cardiac hypertrophy and heart failure. Recently, we also found that not only levels of AM peptide and AM gene expression, but also mRNA levels of CRLR, RAMP2 and RAMP3 are increased in cardiac hypertrophy and failing heart. Cardiac myocytes and fibroblast produce and secrete two molecular forms of AM and express CRLR, RAMP2 and RAMP3, and AM is known to have inhibitory effect of collagen synthesis and antiproliferative effect in cardiac fibroblasts. Stimulation by IL-1beta significantly increased gene expression of AM and its receptor components in cardiac fibroblasts. Preincubated IL-1beta elevated the intracellular cAMP response to exogenous administered AM. AM antisense oligodeoxynucleotide treatment significantly lowered AM levels in cultured medium. IL-1beta significantly increased (3)H-proline incorporation and AM antisense oligodeoxynucleotide treatment further increased (3)H-proline incorporation. Collectively, these results support a protective role for increased AM in the cardiac hypertrophy and heart failure. Then, we tested the effects of acute administration of AM in experimental and human heart failure, because AM has hemodynamic effects including vasodilation, increases in cardiac contractility, cardiac output, diuresis, and natriuresis. We observed profound and sustained cardiovascular, hormonal and renal effects. These effects may incorporate many of the therapeutic goals of heart failure management.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"231-42"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 41
Risk stratification of dyslipidemia: insights from the Framingham Study. 血脂异常的风险分层:来自Framingham研究的见解。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368250
W B Kannel
{"title":"Risk stratification of dyslipidemia: insights from the Framingham Study.","authors":"W B Kannel","doi":"10.2174/1568016054368250","DOIUrl":"https://doi.org/10.2174/1568016054368250","url":null,"abstract":"<p><p>Dyslipidemia, fundamental to the atherosclerotic process, is now a readily correctable risk factor with established efficacy of treatment for reducing risk of CHD and strokes. The current focus on LDL-cholesterol for risk assessment needs to be broadened to accommodate the two-way traffic of cholesterol entering and leaving the arterial intima reflected by the LDL/HDL ratio or the Total/HDL ratio. The choice of lipid therapy should be individualized to take into account the presence of the metabolic syndrome and the lipid profile of the patient. The intensity of therapy and goals should be linked to multivariable risk, particularly in those with modest lipid values. Cardiovascular risk factor clustering is pronounced for each lipid, is promoted by adiposity and greatly influences its CHD hazard. Global risk assessment taking clustering into account is essential for efficient preventive management of lipids. More attention needs to be afforded the absolute risk reduction attainable and must recognize that the number needed to treat to prevent one event increases the lower the lipid value, the lower global risk and the healthier the subject.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"187-93"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 66
Stent-based delivered anti-proliferative drugs in the prevention of coronary stent restenosis. 基于支架的抗增殖药物在预防冠状动脉支架再狭窄中的作用。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368160
Raúl Moreno, Carlos Macaya
{"title":"Stent-based delivered anti-proliferative drugs in the prevention of coronary stent restenosis.","authors":"Raúl Moreno,&nbsp;Carlos Macaya","doi":"10.2174/1568016054368160","DOIUrl":"https://doi.org/10.2174/1568016054368160","url":null,"abstract":"<p><p>Coronary stents are currently used in most percutaneous coronary interventions, since they have demonstrated to reduce restenosis and allow to solve threatened closure after balloon angioplasty. Despite these beneficial effects, restenosis remains as the main limitation of percutaneous coronary interventions even with the use of coronary stents. In the last 3 years, some coronary stents eluting anti-proliferative drugs have demonstrated to dramatically reduce the risk of restenosis. By November 2004, two different types of antiproliferative drugs eluted by coronary stents are commercially available: sirolimus (rapamycin) and paclitaxel. The mechanisms, clinical evidence, as well as the remaining limitations of these drug-eluting stents are reviewed. The current knowledge of other anti-proliferative drugs that are currently under investigation is also reviewed.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"221-9"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Role of cardiovascular aldosterone in hypertension. 心血管醛固酮在高血压中的作用。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368151
Yoshiyu Takeda
{"title":"Role of cardiovascular aldosterone in hypertension.","authors":"Yoshiyu Takeda","doi":"10.2174/1568016054368151","DOIUrl":"https://doi.org/10.2174/1568016054368151","url":null,"abstract":"<p><p>Aldosterone plays an important role in the pathogenesis of cardiovascular disease. We have reported that aldosterone is synthesized in cardiovascular tissues and local aldosterone synthesis plays important roles for hypertension and cardiac hypertrophy. High sodium intake develops and accelerates vascular injury and cardiac hypertrophy in SHRSP. Plasma aldosterone concentrations and PRA were decreased by high salt intake in SHRSP. Aldosterone production, the expression of CYP11B2 mRNA and angiotensin II receptor AT1R mRNA in blood vessels were significantly increased by high salt intake. These results suggest that high salt intake increases aldosterone production and expression of the AT1R mRNA in the vascular tissue in SHRSP, which may contribute to the development of malignant hypertension in salt-loaded SHRSP. However, there are several reports of conflicting data. Mineralocorticoid receptor (MR) binding is tightly regulated by the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which selectively metabolizes glucocorticoids to inactive metabolites, thus allowing for MR activation by aldosterone. We have reported that decreased 11beta-HSD2 in blood vessels in Dahl salt-sensitive (DS) rats, a model for salt-sensitive hypertension. Local aldosterone excess may play a significant role in the salt sensitivity and development of hypertension. High sodium intake decreased circulating rennin-angiotensin-aldosterone system and increased blood pressure and cardiac hypertrophy in DS rats, which were prevented by the treatment with a selective MR antagonist, eplerenone. Eplerenone also improved endothelial nitric oxide synthase (eNOS) activity and eNOS mRNA expression in blood vessels in DS rats. These results further suggest that not only circulating aldosterone but also local aldosterone is of critical importance in the pathophysiology of cardiovascular disorders.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"261-6"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated heart failure: a novel mechanism of drug-induced improvement in contractile performance of the failing heart. 左西孟旦在失代偿性心力衰竭中的抗炎和抗凋亡作用:药物诱导心力衰竭收缩性能改善的新机制。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368232
Ioannis A Paraskevaidis, John T Parissis, Dimitios Th Kremastinos
{"title":"Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated heart failure: a novel mechanism of drug-induced improvement in contractile performance of the failing heart.","authors":"Ioannis A Paraskevaidis,&nbsp;John T Parissis,&nbsp;Dimitios Th Kremastinos","doi":"10.2174/1568016054368232","DOIUrl":"https://doi.org/10.2174/1568016054368232","url":null,"abstract":"<p><p>Recent experimental and clinical observations indicate that over-expression of pro-inflammatory cytokines is actively implicated to chronic heart failure progression through their cytotoxic and negative inotropic effects. Calcium-sensitizing agents, such as levosimendan, promotes inotropy by stabilizing troponin C in a configuration that enhances the calcium sensitivity of cardiac myofilaments, preserving also diastolic relaxation. Levosimendan also opens ATP-dependent potassium channels in peripheral vessels, leading to vasodilatation. Large scale randomized clinical trials have shown that levosimendan administration in patients with severe heart failure due to left ventricular systolic dysfunction results in favorable hemodynamic changes, symptomatic benefit, and a reduction in short-term morbidity and mortality. This review describes current knowledge about novel cellular mechanisms associated with beneficial effects of levosimendan on cardiac contractile performance, focusing mainly on its immunomodulatory and anti-apoptotic properties. Levosimendan-induced improvement in contractile reserve and clinical status of severe heart failure patients, seems to be related with the reduction of major pro-inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling molecules Fas/Fas Ligand. Modulation of pro-inflammatory and pro-apoptotic pathways into the failing heart by levosimendan may be an additional pathophysiologic mechanism that prevents further clinical and hemodynamic consequences of abnormal immune responses in decompensated heart failure and beneficially affects the progression of the syndrome.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"243-7"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 33
Influence of impaired liver methionine metabolism on the development of vascular disease and inflammation. 肝脏蛋氨酸代谢受损对血管疾病和炎症发展的影响。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368197
M A Avila, C Berasain, J Prieto, J M Mato, E R García-Trevijano, F J Corrales
{"title":"Influence of impaired liver methionine metabolism on the development of vascular disease and inflammation.","authors":"M A Avila,&nbsp;C Berasain,&nbsp;J Prieto,&nbsp;J M Mato,&nbsp;E R García-Trevijano,&nbsp;F J Corrales","doi":"10.2174/1568016054368197","DOIUrl":"https://doi.org/10.2174/1568016054368197","url":null,"abstract":"<p><p>Methionine (Met) metabolism involves the sequential formation of S-adenosylmethionine (SAM, the main biological methyl donor), S-adenosylhomocysteine (SAH) and homocysteine (Hcy). Hcy can be remethylated to Met or catabolized through the trans-sulfuration pathway. In mammals, as much as 48% of Met metabolism and up to 85% of all transmethylation reactions occur in the liver. These figures underscore the central role played by this organ in Met metabolism. Maintaining the homeostasis of this metabolic cycle has proved to be essential for the preservation of liver function up to the point of preventing its neoplastic transformation. However, an adequate hepatic metabolism of Met is not only important for the liver parenchymal cell. Evidence has accumulated over the past few years supporting the involvement of Met-derived metabolites in the triggering or attenuation of pathological processes with systemic implications. This is best illustrated by the fact that a deteriorated liver function has emerged as a major factor in the development of hyperhomocysteinemia. Elevated plasma levels of Hcy have been related to several disorders including cardiovascular and cerebrovascular diseases. On the other end, liver damage also leads to deficient SAM synthesis. Among the consequences of impaired SAM synthesis in liver tissue are the enhanced production of pro-inflammatory cytokines and mediators. In this review, we will address the mechanisms and consequences of abnormal Met metabolism in liver injury, the systemic implications of such impairment and finally the potential therapeutic interventions.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"267-81"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25151601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
The pharmacologic approach to the prevention of preeclampsia: from antiplatelet, antithrombosis and antioxidant therapy to anticonvulsants. 预防子痫前期的药理学途径:从抗血小板、抗血栓、抗氧化治疗到抗惊厥药。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368214
J Bar, A Ben-Haroush, D Feldberg, M Hod
{"title":"The pharmacologic approach to the prevention of preeclampsia: from antiplatelet, antithrombosis and antioxidant therapy to anticonvulsants.","authors":"J Bar,&nbsp;A Ben-Haroush,&nbsp;D Feldberg,&nbsp;M Hod","doi":"10.2174/1568016054368214","DOIUrl":"https://doi.org/10.2174/1568016054368214","url":null,"abstract":"<p><p>Preeclampsia has been suggested to be a two-stage disorder of an alteration in placental perfusion (stage 1) leading to generalized vascular endothelial damage (stage 2). Because the mechanism linking the two stages remains unclear, effective primary prevention is still impossible. However, advances made in our understanding of the pathophysiology of preeclampsia have paved the way for secondary and tertiary prevention approaches. Platelets are known to be activated in early pregnancy. They also play a pivotal role in the process of inflammation, as demonstrated by the finding that CD40 ligand is shed from activated platelets to directly initiate inflammation of the vessel wall. According to the Cochrane Library Update summarizing data from over 30,000 women, secondary prevention with antiplatelet drugs is associated with a 19% decrease in the risk of preeclampsia. Additional randomized controlled trials are needed to establish the association between preeclampsia and thrombophilia. The effect of the antithrombotic agent heparin on pregnancy outcome in preeclampsia and its potential preventive action in high-risk patients need to be elucidated. One of the several hypotheses of the pathogenesis of preeclampsia focuses on the oxidative stress caused by the imbalance in prooxidant and antioxidant forces. Preliminary findings on vitamin E and vitamin C supplementation in preeclamptic women are encouraging, and suggest a rationale for larger clinical trials. Although there is currently no explanation for the positive effect of magnesium sulfate on eclamptic seizures, studies have provided enough evidence to encourage its worldwide use as the primary anticonvulsant of choice in the tertiary prevention of maternal and perinatal death in severe preeclampsia/eclampsia. In conclusion, secondary and tertiary prevention of preeclampsia is possible when targeted at reducing maternal and neonatal morbidity and mortality.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"181-5"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: candidate mechanisms for anti-lipid deposition in blood vessels. 3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂的多效作用:血管中抗脂质沉积的候选机制。
Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2005-07-01 DOI: 10.2174/1568016054368223
T Kumai, N Matsumoto, Y Koitabashi, Y Takeba, S Oonuma, S Sekine, M Tadokoro, S Kobayashi
{"title":"Pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: candidate mechanisms for anti-lipid deposition in blood vessels.","authors":"T Kumai,&nbsp;N Matsumoto,&nbsp;Y Koitabashi,&nbsp;Y Takeba,&nbsp;S Oonuma,&nbsp;S Sekine,&nbsp;M Tadokoro,&nbsp;S Kobayashi","doi":"10.2174/1568016054368223","DOIUrl":"https://doi.org/10.2174/1568016054368223","url":null,"abstract":"<p><p>The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are considered first-line therapeutic agents for the prevention of coronary heart disease and atherosclerotic disorders related to hypercholesterolemia. Statins inhibit lipid deposition in the aortic endothelium. Although it has been accepted that the statins are potent inhibitors of cholesterol biosynthesis in the liver and that they lower circulating cholesterol levels, several cholesterol-independent (pleiotropic) effects have been reported. The cholesterol-independent effects of statins involve normalization of the nitric oxide (NO)-NO synthase system, anti-inflammatory effects through the inhibition of cytokine/chemokine production, inhibition of vascular smooth muscle cell proliferation and migration, and inhibition of platelet thrombus formation/reduction of the thrombotic response. Some pleiotropic effects of statins may depend on the inhibition of the biosynthesis of farnesyl- and geranylgeranyl-nonsterol compounds from mevalonate in the cells. The Rho/Rho kinase pathway and the phospatidylinositol-3 kinase/Akt pathway mediate the pleiotropic effects of statins. As variations occur in absorption, metabolism, and excretion mechanisms due to the characteristics of specific statins including their hydrophilicity and lipophilicity, there are differences in the transfer mechanisms of statins into tissues. However, the pleiotropic effects occur regardless of statin hydrophilicity and lipophilicity. This review summarizes the pleiotropic effects of statins on lipid deposition in blood vessels.</p>","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"3 3","pages":"195-201"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016054368223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25152834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
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