microRNAs在高血压疾病中的作用机制

高血压作为一种多因素的慢性疾病,其引起的一系列并发症是导致心血管疾病死亡的主要原因。微RNA（microRNA,miRNAs）作为内源性单链非编码RNA,在高血压的病理生理过程中发挥重要作用。miRNAs通过调控血管内皮细胞损伤、血管平滑肌细胞功能障碍、单核/巨噬细胞介导的免疫炎症反应、氧化应激、一氧化氮合成异常、肾素 血管紧张素 醛固酮系统的激活、交感神经激活、肾水钠潴留和胰岛素抵抗等过程,进而广泛参与高血压的发病过程。本文就miRNAs在高血压发生发展中的作用机制及其研究进展进行简要综述,为高血压早期诊断及治疗提供新思路。     

High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro

Magnesium supplementation has been reported to prevent cardiovascular diseases through the decrease of plasma lipids and to improve endothelial function in patients with coronary artery disease. In the present work, we evaluated whether high magnesium concentrations can directly affect the function of cultured endothelial cells, which play a crucial role in maintaining the functional integrity of the vascular wall. We cultured human umbilical vein endothelial cells for various times in media containing different concentration of magnesium (range 2 to 10 mM) and compared them to the corresponding controls (1 mM Mg). High Mg concentrations stimulated endothelial proliferation, enhanced the motogenic response to angiogenic factors and attenuated the response to lipopolysaccharide (LPS). In addition, we demonstrate that high concentrations of magnesium did not modulate the levels of plasminogen activator inhibitor-1, but enhanced the synthesis of nitric oxide, in part through the up-regulation of endothelial nitric oxide synthase. Our results demonstrate a direct role of magnesium in maintaining endothelial function. We therefore anticipate that magnesium may have a protective effect against atherosclerosis and could play a role in promoting the growth of collateral vessels in chronic ischemia. Moreover, because it induces the synthesis of nitric oxide, this cation could be a helpful tool in hypertension as well as in preventing thrombosis.     

Clinical aspects of reactive oxygen and nitrogen species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.     

HZE ⁵⁶Fe-ion irradiation induces endothelial dysfunction in rat aorta: role of xanthine oxidase

Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage.     

S-Nitrosothiols—NO donors regulating cardiovascular cell proliferation: Insight into intracellular pathway alterations

Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) activates signaling pathways responsible for smooth muscle cell relaxation, leading to vasodilation and thus plays an important role in controlling vascular homeostasis, thrombosis and inflammation.Recent studies indicate that S-nitrosothiols produced in vivo as well as synthetic ones might be important reservoirs of NO. Based on a broad range of NO functions within the living organisms, this review highlights the impact of S-nitrosothiols on cardiovascular cell cycle. The cell membrane transport and the decomposition patterns responsible of S-nitrosothiols actions are presented. The effects of NO delivery through S-nitrosothiols have a significant potential in cardiovascular diseases with various underlying causes. The challenges related to their application in the pharmacotherapy of patients with various cardiovascular diseases are also discussed.     

Chronic administration of NMU into the paraventricular nucleus stimulates the HPA axis but does not influence food intake or body weight

C-reactive protein (CRP), a predictor of future cardiovascular diseases, has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation. This proatherogenic CRP was speculated to have a role in attenuating angiogenic functions of human endothelial progenitor cells (EPCs), possibly impairing vascular regeneration and increasing cardiovascular vulnerability to ischemic injury. Herein, we investigated the direct effect of CRP on angiogenic activity and gene expression in human EPCs. Incubation of EPCs with human recombinant CRP significantly inhibited EPC migration in response to vascular endothelial growth factor, possibly by decreasing the expression of endothelial nitric oxide synthase and subsequent nitric oxide production. In addition, CRP-treated EPCs showed the reduced adhesiveness onto an endothelial cell monolayer. When assayed for the gene expression of arteriogenic chemo-cytokines, CRP substantially decreased their expression levels in EPC, in part due to the upregulation of suppressors of cytokine signaling proteins. These results suggest that CRP directly attenuates the angiogenic and possibly arteriogenic functions of EPCs. This CRP-induced EPC dysfunction may impair the vascular regenerative capacity of EPCs, thereby leading to increased risk of cardiovascular diseases.     

Cell biology and lipoproteins in atherosclerosis

Atherosclerosis is an inflammatory process, triggered by the presence of lipids in the vascular wall, and encompasses a complex interaction among inflammatory cells, vascular elements, and lipoproteins through expression of several adhesion molecules and cytokines. Subendothelial retention of lipoproteins is the key initiating event in atherosclerosis, provoking a cascade of events to pathogenic response. High levels of plasma lipids, particularly low-density (LDL) and very-low-density lipoproteins (VLDL) are among the pathophysiologic stimuli that induce endothelial dysfunction. Endothelial cells regulate coagulation, thrombosis and the fibrinolytic system; the endothelium modulates the activity of smooth muscle cells (vascular tone/proliferation) and controls the traffic of macromolecules and inflammatory cells to the vessel wall. Furthermore, LDLs have been implicated in the induction of changes in permeability, cell adhesion and secretion of vasoactive molecules (nitric oxide [NO]), while VLDLs seem to modulate the fibrinolytic system [tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)]. In this review, we will focus on the pathophysiologic functions of lipoproteins in the vascular wall.     

Oxidative stress in patients with cardiovascular disease and chronic renal failure

Abstract

Oxidative response regulates many physiological response in human health, but if not properly regulated it could also lead to a number of deleterious effects. The importance of oxidative stress injury depends on the molecular target, the severity of the stress, and the mechanism by which the oxidative stress is imposed: it has been implicated in several diseases including cancer, neurodegenerative diseases, malaria, rheumatoid arthritis and cardiovascular and kidney disease. Most of the common diseases, such as hypertension, atherosclerosis, heart failure, and renal dysfunction, are associated with vascular functional and structural alterations including endothelial dysfunction, altered contractility, and vascular remodeling. Common to these processes is increased bioavailability of reactive oxygen species (ROS), decreased nitric oxide (NO) levels, and reduced antioxidant capacity. Oxidative processes are up-regulated also in patients with chronic renal failure (CRF) and seem to be a cause of elevated risk of morbidity and mortality in these patients.

In this review, we highlight the role of oxidative stress in cardiovascular and renal disease.     

Protective effects of AMP‐activated protein kinase in the cardiovascular system

Cardiovascular diseases remain the leading cause of mortality worldwide. Recent studies of AMP-activated protein kinase (AMPK), a highly conserved sensor of cellular energy status, suggest that there might be therapeutic value in targeting the AMPK signaling pathway. AMPK is found in most mammalian tissues, including those of the cardiovascular system. As cardiovascular diseases are typically associated with blood flow occlusion and blood occlusion may induce rapid energy deficit, AMPK activation may occur during the early phase upon nutrient deprivation in cardiovascular organs. Therefore, investigation of AMPK in cardiovascular organs may help us to understand the pathophysiology of defence mechanisms in these organs. Recent studies have provided proof of concept for the idea that AMPK is protective in heart as well as in vascular endothelial and smooth muscle cells. Moreover, dysfunction of the AMPK signalling pathway is involved in the genesis and development of various cardiovascular diseases, including atherosclerosis, hypertension and stroke. The roles of AMPK in the cardiovascular system, as they are currently understood, will be presented in this review. The interaction between AMPK and other cardiovascular signalling pathways such as nitric oxide signalling is also discussed.     

Bridging advanced glycation end product, receptor for advanced glycation end product and nitric oxide with hormonal replacement/estrogen therapy in healthy versus diabetic postmenopausal women: a perspective

Cardiovascular diseases (CVD) are the most significant cause of death in postmenopausal women. The loss of estrogen biosynthesis with advanced age is suggested as one of the major causes of higher CVD in postmenopausal women. While some studies show beneficial effects of estrogen therapy (ET)/hormonal replacement therapy (HRT) in the cardiovascular system of healthy postmenopausal women, similar studies in diabetic counterparts contradict these findings. In particular, ET/HRT in diabetic postmenopausal women results in a seemingly detrimental effect on the cardiovascular system. In this review, the comparative role of estrogens is discussed in the context of CVD in both healthy and diabetic postmenopausal women in regard to the synthesis or expression of proinflammatory molecules like advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGEs), inducible nitric oxide synthases (iNOS) and the anti-inflammatory endothelial nitric oxide synthases (eNOS). The interaction of AGE-RAGE signaling with molecular nitric oxide (NO) may determine the level of reactive oxygen species (ROS) and influence the overall redox status of the vascular microenvironment that may further determine the ultimate outcome of the effects of estrogens on the CVD in healthy versus diabetic women.     

Mechanisms linking angiotensin II and atherogenesis

PURPOSE OF REVIEW: The concept that angiotensin II plays a central role in early atherogenesis, progression to atherosclerotic plaque, and the most serious clinical sequelae of coronary artery disease is the subject of considerable current interest. Results from recent large clinical trials confirm that blunting of the renin-angiotensin system through either angiotensin converting enzyme inhibition or angiotensin II type 1 receptor blockade incurs significant beneficial outcomes in patients with coronary artery disease. The exact mechanisms for these effects are not yet clear, but are suggested by studies demonstrating that suppression of the renin-angiotensin system is associated with muted vascular oxidative stress. RECENT FINDINGS: As most of the biological effects of the renin-angiotensin system occur through stimulation of the angiotensin II type 1 receptor, the focus of this review is on changes in the vascular wall mediated by this receptor and primarily related to endothelial and vascular smooth muscle cells, monocyte/macrophages and platelets. The interactions between angiotensin II and nitric oxide exert particular demands on the vascular capacity to adapt to dyslipidemia, hypertension, estrogen deficiency and diabetes mellitus that appear to exacerbate atherogenesis. Associated with each of these conditions is angiotensin II-mediated stimulation of macrophages, platelet aggregation, plasminogen activator inhibitor 1, endothelial dysfunction, vascular smooth muscle cell proliferation and migration, apoptosis, leukocyte recruitment, fibrogenesis and thrombosis. SUMMARY: Inhibition of the actions of angiotensin II serves a dual purpose: indirectly through reduction of mechanical stress on the vascular wall, and directly by diminished stimulation for vascular restructuring and remodeling. Collectively, data from studies published over the last year confirm and extend the notion that angiotensin II is a true cytokine prevalent at all stages of atherogenesis.     

The role of nitric oxide in cardiovascular diseases

Nitric oxide (NO) is a gaseous lipophilic free radical cellular messenger generated by three distinct isoforms of nitric oxide synthases (NOS), neuronal (nNOS), inducible (iNOS) and endothelial NOS (eNOS). NO plays an important role in the protection against the onset and progression of cardiovascular disease. Cardiovascular disease is associated with a number of different disorders including hypercholesterolaemia, hypertension and diabetes. The underlying pathology for most cardiovascular diseases is atherosclerosis, which is in turn associated with endothelial dysfunctional. The cardioprotective roles of NO include regulation of blood pressure and vascular tone, inhibition of platelet aggregation and leukocyte adhesion, and prevention smooth muscle cell proliferation. Reduced bioavailability of NO is thought to be one of the central factors common to cardiovascular disease, although it is unclear whether this is a cause of, or result of, endothelial dysfunction. Disturbances in NO bioavailability leads to a loss of the cardio protective actions and in some case may even increase disease progression. In this chapter the cellular and biochemical mechanisms leading to reduced NO bioavailability are discussed and evidence for the prevalence of these mechanisms in cardiovascular disease evaluated.     

Genetics of thrombophilia: impact on atherogenesis

PURPOSE OF REVIEW: The goal of this review is to present an update on basic and epidemiological findings associating variants in prothrombotic genes with atherogenesis and atherothrombotic disease. RECENT FINDINGS: The relation between atherosclerosis and thrombosis has long been recognized but only recently has it been understood that certain hemostatic factors affect not only thrombus formation, but also have a direct atherogenic role. Atherosclerosis is a complex disorder that results from the interaction of multiple genetic and environmental factors. Numerous polymorphisms and mutations in genes related to the hemostatic system and to vascular redox determinants that modulate nitric oxide bioavailability have been identified in the past decade; their role in atherogenesis and the risk of cardiovascular disease, however, remain uncertain. We will discuss the functional implications and association with disease risk of polymorphisms in coagulation factors (fibrinogen, prothrombin, and factor V); fibrinolytic factors (plasminogen activator inhibitor 1 and lipoprotein(a)); platelet surface receptors; and vascular redox determinants (methylenetetrahydrofolate reductase, endothelial nitric oxide synthase, and the antioxidant enzymes cellular glutathione peroxidase and paraoxonase). SUMMARY: Overall, these genetic variants have a modest effect on risk when considered individually but gain potency when acting synergistically with other genetic or environmental risk factors. We conclude that a better characterization of these interactions, in addition to the identification of potential novel genetic determinants, constitute key issues in the future understanding of the pathogenesis of atherothrombosis.     

Physiological role of ROCKs in the cardiovascular system

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits. Rho GTPase; Rho-kinase; vascular endothelium; contraction; actin cytoskeleton; nitric oxide; statins     

ADMA-- 一个新的心血管疾病危险因子

非对称性二甲基精氨酸(asymmetric dimethylarginine,ADMA)为内源性一氧化氮合酶(endogenous Nitric-Oxide Synthase,eNOS)竞争性抑制剂,可抑制NOS的活性,减少一氧化氮(nitric oxide,NO)的合成,致使内皮功能障碍。近年来研究认为ADMA是冠心病的独立预测因子,与心功能不全及心血管疾病死亡率明显相关。本文将针对ADMA与心血管疾病的相关性进行综述。     

Signaling across myoendothelial gap junctions--fact or fiction?

Gap junctions interconnect vascular cells homocellularly, thereby allowing the spread of signals along the vessel wall, which serve to coordinate vessel behavior. In addition, gap junctions provide heterocellular coupling between endothelial and vascular smooth muscle cells, creating so-called myoendothelial gap junctions (MEGJs). Endothelial cells control vascular tone by the release of factors that relax vascular smooth muscle. Endothelial factors include nitric oxide, prostaglandins, and an additional dilator principle, which acts by smooth muscle hyperpolarization and is therefore named endothelium-derived hyperpolarizing factor (EDHF). Whether this principle indeed relies on a factor or on intact MEGJs, which allow direct current transfer from endothelial to smooth muscle cells, has recently been questioned. Careful studies revealed the presence of vascular cell projections that make contact through the internal elastic lamina, exhibit the typical GJ morphology, and express connexins in many vessels. The functional study of the physiological role of MEGJs is confined by the difficulty of selectively blocking these channels. However, in different vessels studied in vitro, the dilation related to EDHF was sensitive to experimental interventions that block MEGJs more or less specifically. Additionally, bidirectional electrical coupling between endothelial and smooth muscle cells was demonstrated in isolated small vessels. In marked contrast, similar approaches used in conjunction with intravital microscopy, which allows examination of vascular behavior in the intact animal, did not verify electrical or dye-coupling in different models investigated. The discrepancy between in vitro and in vivo investigations may be due to size and origin of the vessels studied using these distinct experimental approaches. Additionally, MEGJ coupling is possibly tightly controlled in vivo by yet unknown mechanisms that prevent unrestricted direct signaling between endothelial and smooth muscle cells.     

Effects of a dammarane-type saponin,ginsenoside Rd,in nicotine-induced vascular endothelial injury

BackgroundPanax notoginseng (Burk.) F.H. Chen is a traditional medicinal plant widely used to prevent and treat cardiovascular diseases. Ginsenoside Rd (GRd) is a major bioactive component of P. notoginseng, but specific effects on cardiovascular disease-related pathogenic processes are rarely studied, especially vascular endothelial injury.PurposeThis study investigated the potential protective efficacy of GRd against nicotine-induced vascular endothelial cell injury, disruption of vascular nitric oxide (NO) signaling, aberrant endothelium–monocyte adhesion, platelet aggregation, and vasoconstriction.Study design/MethodsVascular endothelial injury and functional disruption were investigated in cultured human umbilical vein endothelial cells (HUVECs) by biochemical assays for nitric oxide (NO) and angiotensin II (Ang II), immunofluorescence (IF) and western blotting for expression analyses of apoptosis- related proteins, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Ang II type receptor 1 (AGTR1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). In addition, vascular protection by GRd was examined in nicotine-administered Sprague-Dawley (SD) rats by serum NO and Ang II assays, and by hematoxylin-eosin (HE) and immunostaining of aorta. We also examined effects of GRd on monocyte (THP-1 cells) adhesion assays, adenosine diphosphate (ADP)-induced platelet aggregation, and phenylephrine (PE)-induced vasoconstriction of isolated rat aortic rings.ResultsIn HUVECs, nicotine significantly suppressed NO production, enhanced Ang II production, downregulated eNOS expression, and upregulated expression levels of AGTR1, TLR4, MyD88, NF-κB, iNOS, Bax/Bcl-2 ratio, cleaved caspase-3, and cytochrome c (cyt c). All of these changes were significantly reversed by GRd. In rats, oral GRd reversed the reduction NO and enhanced Ang II production in serum induced by nicotine administration, and HE staining revealed protection of aortic endothelial cells. In addition, GRd reversed nicotine-mediated enhancement of HUVECs-monocyte adhesion, inhibited ADP-induced platelet aggregation and PE-induced vasoconstriction.ConclusionGRd may prevent nicotine-induced cardiovascular diseases by preserving normal vascular endothelial NO signaling, suppressing platelet aggregation and vasoconstriction, and by preventing endothelial cell–monocyte adhesion.     

Thrombospondin-1 and CD47 regulation of cardiac,pulmonary and vascular responses in health and disease

Cardiovascular homeostasis and health is maintained through the balanced interactions of cardiac generated blood flow and cross-talk between the cellular components that comprise blood vessels. Central to this cross-talk is endothelial generated nitric oxide (NO) that stimulates relaxation of the contractile vascular smooth muscle (VSMC) layer of blood vessels. In cardiovascular disease this balanced interaction is disrupted and NO signaling is lost. Work over the last several years indicates that regulation of NO is much more complex than previously believed. It is now apparent that the secreted protein thrombospondin-1 (TSP1), that is upregulated in cardiovascular disease and animal models of the same, on activating cell surface receptor CD47, redundantly inhibits NO production and NO signaling. This inhibitory event has implications for baseline and disease-related responses mediated by NO. Further work has identified that TSP1-CD47 signaling stimulates enzymatic reactive oxygen species (ROS) production to further limit blood flow and promote vascular disease. Herein consideration is given to the most recent discoveries in this regard which identify the TSP1-CD47 axis as a major proximate governor of cardiovascular health.     

Asymmetric Dimethylarginine (ADMA) and other Endogenous Nitric Oxide Synthase (NOS) Inhibitors as an Important Cause of Vascular Insulin Resistance

Asymmetric dimethylarginine (ADMA) and NG-monomethyl- L-arginine ( L-NMMA) are important endogenous endothelial nitric oxide synthase (eNOS) inhibitors. Studies have shown that patients with insulin resistance have elevated plasma levels of ADMA. Moreover, ADMA levels have a prognostic value on long-term outcome of patients with coronary artery disease. Insulin resistance, a disorder associated to inadequate biological responsiveness to the actions of exogenous or endogenous insulin, is a metabolic condition, which exists in patients with cardiovascular diseases. This disorder affects the functional balance of vascular endothelium via changes of nitric oxide (NO) metabolism. Nitric oxide is produced in endothelial cells from the substrate L-arginine via eNOS. Elevated ADMA levels cause eNOS uncoupling, a mechanism which leads to decreased NO bioavailability and increased production of hydrogen peroxide. According to clinical studies, the administration of L-arginine to patients with high ADMA levels improves NO synthesis by antagonizing the deleterious effect of ADMA on eNOS function, although in specific populations such as diabetes mellitus, this might even been harmful. More studies are required in order to certify the role of NOS inhibitors in insulin resistance and endothelial dysfunction. It is still difficult to say whether increased ADMA levels in certain populations is only a reason or the result of the molecular alterations, which take place in vascular disease states.     

Inflammation,oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.