{"id":313,"date":"2018-12-01T10:21:15","date_gmt":"2018-12-01T10:21:15","guid":{"rendered":"http:\/\/www.gyanvihar.org\/journals\/?p=313"},"modified":"2018-12-19T09:51:37","modified_gmt":"2018-12-19T09:51:37","slug":"atherosclerosis-inflammation-and-oxidative-stress-2","status":"publish","type":"post","link":"https:\/\/www.gyanvihar.org\/journals\/atherosclerosis-inflammation-and-oxidative-stress-2\/","title":{"rendered":"ATHEROSCLEROSIS, INFLAMMATION AND OXIDATIVE STRESS"},"content":{"rendered":"

pp<\/strong>.17-29,<\/strong><\/span><\/p>\n

Pratibha K. Jain* and Suresh C. Joshi<\/strong><\/span><\/p>\n

Center for advanced studies, Department of Zoology University of Rajasthan, Jaipur \u2013 302 055 (India)<\/span><\/p>\n

*<\/em>Corresponding Author Email:\u00a0pratibha.721@gmail.com<\/a><\/span><\/p>\n

ABSTRACT<\/span><\/h2>\n

Atherosclerosis is a focal disease of the arterial wall that leads to cardiovascular disease (CVD), the biggest cause of morbidity and mortality in Western societies. CVD, a group of disorders of the heart and the vasculature, includes atherosclerosis, high blood pressure, coronary heart disease, congestive heart failure, stroke and congenital heart defects. The World Health Organization report emphasizes that the cardio vascular diseases to be the leading cause of death and disability in India by 2020. Atherosclerosis with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk of future cardiovascular events. Furthermore during the last decades several studies have examined the potential role of oxidative stress in atherogenesis. Atherosclerosis and cardiovascular disease take a substantial tax on our society. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Moreover, presently there is an increasing interest worldwide in herbal medicines accompanied by increased laboratory investigation into the pharmacological properties of the bioactive ingredients and their ability to treat various diseases.<\/span><\/p>\n

K<\/strong>e<\/strong>y Words<\/strong>: Atherosclerosis, Inflammation, Oxidative stress, CRP, Antioxidant<\/span><\/p>\n

INTRODUCTION<\/span><\/h2>\n

More than 25 million persons in the United States have at least one clinical manifestation of atherosclerosis and in many more, atherosclerosis remains an occult but imperative forerunner of significant cardiovascular events. Atherosclerosis is the preliminary lipid disorders that affect large and medium-sized muscular arteries and is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids,\u00a0 \u00a0cholesterol,\u00a0 \u00a0calcium,\u00a0 \u00a0and\u00a0 \u00a0cellular debris within the intima of the vessel wall. This \u00a0buildup \u00a0results \u00a0in \u00a0plaque \u00a0formation, vascular\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 remodeling,\u00a0 acute and\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 chronic luminal obstruction, abnormalities of blood flow and diminished oxygen supply to target organs\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 (Bibave\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 et\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 al.,\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 2011).\u00a0 Disease progression\u00a0\u00a0\u00a0\u00a0 can\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 lead\u00a0 eventually\u00a0 to\u00a0 the occurrence \u00a0of \u00a0acute \u00a0cardiovascular \u00a0events such\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 as\u00a0 myocardial\u00a0 infarction,\u00a0\u00a0\u00a0\u00a0\u00a0 unstable angina pectoris and sudden cardiac death. Atherosclerosis \u00a0(AS), \u00a0hardening \u00a0(Sclerosis) of the arteries (athero) is a slowly progressing chronic disorder of medium and large- sized arteries result in to plaque formation in the walls of the vessels. Arterial plaque consists of cholesterol, fat deposits, calcium, cellular waste products and excess fluid, which can block off an artery or decrease the rate of blood flow throughout the entire body (Livingston and Lynm, 2012). AS is recognized as a subacute inflammatory condition of the arterial vessel wall characterized by infilteration of T-cells and macrophages which interact with one another and with arterial wall cells (Wildgruber et al., 2013). AS and CVD initiates with the movement of oxidized low-density lipoproteins (OxLDL) to the intima (Subendothelial space) causing injury to endothelial cells (Melo et al., 2011). The pathogenesis of atherosclerosis can be accelerated when there is an imbalance between oxidative stress and the antioxidant defence mechanisms (Griendling and FitzGerald, 2003). Atherosclerosis with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation.<\/span><\/p>\n

INFLAMMATION AND ATHEROSCLEROSIS<\/span><\/h2>\n

Atherosclerosis is characterized by a complex multifactorial pathophysiology. Inflammation is \u00a0widely \u00a0considered \u00a0to \u00a0be \u00a0an important contributing factor of the pathophysiology of coronary heart disease (CHD), and the inflammatory cascade is particularly important in the atherosclerotic process. Inflammation in the vessel wall is now considered to play an essential role in the initiation, progression and the final steps of atherosclerosis, namely \u00a0plaque destabilization and eventually plaque rupture. Histologically atheromatous plaques obtained at autopsy have demonstrated the presence of inflammatory mononuclear cells with foci of monocytes, macrophages and T lymphocytes in the arterial wall. From a pathological point of view, all stages of the atherosclerotic process, from its initiation to plaque rupture, might be considered an inflammatory response to injury and endothelial dysfunction. Damage to the endothelial wall triggers a cascade of events that modulates the inflammatory response, leading to the recruitment of white blood cells into the blood vessel wall, where they give rise to abnormal foam cells and initiate the development of atherosclerotic lesions (Pf\u00fctzner et al., 2010).<\/span><\/p>\n

Inflammatory markers<\/span><\/h2>\n

The notion of atherosclerosis as an inflammatory disease is based on the finding that immune competent cells are abundant in atherosclerotic lesions, and also are producing cytokines, especially proinflammatory cytokines (Frostegard et al., 1999). C-reactive protein level is a strong predictor of cardiovascular events, even more than LDL cholesterol (Ridker et al., 2002). The inflammatory processes are considered to be critical determinants of pathological alterations of the vasculature such as thickening of vessel wall, fatty streak formation, or promotion of atherosclerotic plaques. In consideration of the important role that inflammatory processes play in determining plaque stability, recent work has focused on whether biomarkers of inflammation may help to improve risk\u00a0 stratification and identify patient groups who might benefit from particular treatment strategies. Among them, CRP is an excellent biomarker of inflammation and plays a pivotal role in many aspects of atherogenesis including, activation of complement pathway, lipids uptake by macrophage, release of proinflammatory cytokines, induces the expression of tissue factor in monocytes, promotes the endothelial dysfunction and inhibits nitric oxide production. Many large- scale prospective studies demonstrate that CRP strongly and independently predicts adverse cardiovascular events.<\/span><\/p>\n

OX<\/strong>IDATIVE STRESS AND ATHEROSCLEROSIS<\/strong><\/span><\/p>\n

Oxidative stress have been reported to play an important role in the pathogenesis and development of cardiovascular diseases, including atherosclerosis (Rizzo et al., 2009). Free radicals which possess an unpaired electron in their outermost shell and are capable of independent existence. Their half- lives vary from a few nanoseconds for the most reactive compounds to seconds and hours for rather stable radicals. They trigger chain reactions resulting in the oxidation of macromolecules in order to reach a steady state. Indirect evidence via observing biomarkers such as reactive oxygen species, and reactive nitrogen species production, antioxidant defense indicates oxidative damage may be involved in the pathogenesis of atherosclerosis (Yudoh et al., 2005).<\/span><\/p>\n

Oxidative modification hypothesis\u00a0<\/strong>: The oxidative modification hypothesis, based on the concept that LDL becomes entrapped in the subendothelial space where it is subject to oxidative modification by resident vascular cells such as smooth muscle cells, endothelial cells, and macrophages. Accordingly, oxidized LDL contributes to atherogenesis by Stimulating monocyte chemotaxis- aiding the recruitment of circulating monocytes into the intimal space<\/span><\/p>\n