Timely topics in medicine. Cardiovascular diseases最新文献

The main cause of erectile dysfunction is organic in nature, with vascular etiologies being the most common risk factors. The incidence of erectile dysfunction increases with the number of vascular comorbidities such as hypertension, diabetes, hyperlipidemia, smoking and atherosclerosis. The earliest signal of endothelial damage in men with vascular risk factors is the manifestation of erectile dysfunction. The penis is a barometer of the body's endothelial function, so it is reasonable then to correlate vascular pathologies as direct causes of erectile dysfunction. Moreover, erectile dysfunction may be the first clinical presentation of any of these comorbidities, with the vascular endothelium playing a pivotal role in regulating vascular homeostasis of the corpora cavernosa. This article addresses the impact of vascular risk factors on erectile function based on current evidence.

The renin-angiotensin-aldosterone axis is an integral component linking the renal-humoral system to the cardiovascular system. It is involved in the normal control of blood pressure and intravascular volume. Its activity is also enhanced in pathologic states, namely congestive heart failure, in which stimulation of the axis leads to further deleterious effects on the heart. The well-established dogma that the renin-angiotensin-aldosterone system (RAAS) is a linear cascade is evolving into a vision of this system as a more complex process. It is now known that angiotensin has several subtypes. Each subtype is a ligand at several receptor subtypes and these interactions are not mutually exclusive. The aim of this review is to discuss the different angiotensin subtypes, their receptor interactions and their pathophysiological roles in humoral and renal functions in congestive heart failure. In addition, we will also review the different therapeutic approaches that interrupt the RAAS and the evidence that supports their utility in congestive heart failure (CHF).

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPARs have three isoforms, alpha, beta (or delta) and gamma. It has been conceived that PPARgamma is expressed predominantly in adipose tissue and promotes adipocyte differentiation and glucose homeostasis. Recently, synthetic antidiabetic thiazolidinediones and natural prostaglandin D2 (PGD2) metabolite, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), have been identified as ligands for PPARgamma. Following demonstration that PPARgamma is present in a variety of cell types, further study of PPARgamma has been conducted. Although activation of PPARgamma appears to have beneficial effects on atherosclerosis and heart failure, it is still largely uncertain whether PPARgamma ligands prevent the development of cardiovascular diseases. Recent evidence suggests that some benefit from the antidiabetic agents known as thiazolidinediones may occur through PPARgamma-independent mechanisms. In this review, we report on the latest developments concerning the study of PPARs and summarize the roles of the PPARgamma-dependent pathway in cardiovascular diseases.

Statins reduce cholesterol levels through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme that regulates cholesterol synthesis. The cholesterol-lowering effect of statins is also due to an increase in the uptake of cholesterol by cells as a result of intracellular cholesterol depletion and enhanced expression of low-density lipoprotein (LDL) receptors. The use of statins as lipid-lowering agents has lead to remarkable changes in the treatment and prevention of ischemic heart disease. Results of large clinical trials of patients with ischemic heart disease have demonstrated that statins reduce inflammatory markers such as C-reactive protein, an independent risk factor in the disease. Statins exhibit properties that are beyond their lipid-lowering effects. These non-lipid-lowering properties involve the inhibition of the isoprenoid pathway through decreased synthesis of many nonsteroidal isoprenoid compounds. The focus on the immunomodulatory effect of statins is the result of the positive outcome of pravastatin treatment in cardiac transplantation patients, as well as angiographic regression studies showing insignificant changes in the degree of coronary stenosis despite a large reduction in cardiac events. Statin treatment reduces the risk of ischemic stroke despite the fact that LDL cholesterol is not directly associated with the risk of stroke. This observation lead to the investigation of the role of statins in inflammation and the immune system. Recent research data demonstrated that statins inhibit the induction of the major histocompatibility (MHC) class II expression by interferon-gamma (IFN-gamma), leading to repression of MHC II-mediated T-cell activation. Furthermore, statins inhibit the expression of specific cell surface receptors on monocytes, adhesion molecules and also integrin-dependent leucocyte adhesion. While statins may stimulate the secretion of caspase-1, IL-1beta and IL-18 in peripheral mononuclear cells in response to Mycobacterium tuberculosis, they exhibit additional effects on inflammation by decreasing IL-6 synthesis in human vascular smooth muscle cells (VSMC) in vitro. The focus of this monograph is to highlight the role of statins in the modulation of the immune system and inflammatory processes.

There are many drug interactions with antihypertensive agents and some of these are highly significant. Patients with hypertension frequently take multiple medications and may be at increased risk for drug interactions. Nearly every elderly patient with multiple medical problems will have the potential for one drug interaction in their regimen. These drug interactions can lead to morbidity or even mortality if appropriate steps are not taken to minimize this risk. Drug interactions may occur due to pharmacokinetic (i.e., absorption, distribution, metabolism, elimination) or pharmacodynamic interactions. Physicians and pharmacists must remain vigilant in their monitoring of potential drug interactions and make appropriate dosage or therapy adjustments.

Statins, a group of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used in clinical practice for their efficacy in producing significant reductions in plasma cholesterol and LDL cholesterol and in reducing morbidity and mortality from cardiovascular disease. However, several large clinical trials have suggested that the cholesterol-lowering effects of statins may not completely account for the reduced incidence of cardiovascular disease seen in patients receiving statin therapy. A number of recent reports have shown that statins may also have important antiinflammatory effects, in addition to their effects on plasma lipids. Since inflammation is closely linked to the production of reactive oxygen species (ROS), the molecular basis of the observed antiinflammatory effects of statins may relate to their ability block the production and/or activity of ROS. In this review, we will discuss both the inhibition of ROS generation by statins, through interference with NAD(P)H oxidase expression and activity, and the actions of statins that serve to blunt the damaging effects of these radicals, including effects on antioxidant enzymes, lipid peroxidation, LDL cholesterol oxidation and nitric oxide synthase. These antioxidant effects of statins likely contribute to their clinical efficacy in treating cardiovascular disease as well as other chronic conditions associated with increased oxidative stress in humans.