Biochemical Evidence of Atherosclerosis Progression Mediated by Increased Oxidative Stress in Apolipoprotein E–Deficient Spontaneously Hyperlipidemic Mice Exposed to Chronic Cigarette Smoke

Abstract

Abstract. Cigarette smoking is a major risk factor for cardiovascular disease. The induction of oxidative stress by smoking plays a key role in the progression of atherosclerosis. However, the underlying mechanisms are not fully understood. In the present study, we investigated whether long-term smoking can accelerate the progression of atherosclerosis and whether oxidative stress is implicated in its pathogenesis. Apolipoprotein E-deficient spontaneously hyperlipidemic mice, a model of atherosclerosis, were exposed to the gas-phase of smoke, from which tar and nicotine had been removed, for 15 min a day, 6 days a week, for 16 weeks. Exposure to cigarette smoke significantly increased the serum levels of oxidative stress markers such as thiobarbituric acidreactive substances, oxidatively modified low-density lipoproteins, and 3-nitrotyrosine, but it did not affect serum cholesterol and triglyceride levels. Exposure to smoke also accelerated the accumulation of total cholesterol levels in the aorta that was accompanied by an increase in 3-nitrotyrosine levels of the atherosclerotic mice. These changes in the serum and aorta that progressed with exposure to smoke were prevented by vitamin E administration. Our data suggest that chronic cigarette smoking promotes and aggravates atherosclerosis and that the antioxidant vitamin E exerts an anti-atherogenic effect via reduction of oxidative stress.

<b>Trans-resveratrol reduces cardiac oxidative stress in rats exposed to cigarette smoke

“…The mainstream exposure to cigarette smoke is equivalent to the active smoking, which is composed of about 8% of tar and 92% of gaseous components that contain or induce the formation of ROS (SMITH; FISCHER, 2001). The exposure to cigarette smoke affects a wide variety of oxidizing compounds, such as ROS, which promotes the oxidation of lipids of the cell membrane and increases the systemic oxidative stress (KUNITOMO et al, 2009). Lipid peroxidation leads to a decrease in the membrane fluidity and alignment of receivers, which interferes in the transport and provokes rupture and cell lysis (MACHLIN;BANDICH, 1987).…”

“…The exposure to cigarette smoke affects a wide variety of oxidizing compounds, such as ROS, which promotes the oxidation of lipids of the cell membrane and increases the systemic oxidative stress (KUNITOMO et al, 2009). Lipid peroxidation leads to a decrease in the membrane fluidity and alignment of receivers, which interferes in the transport and provokes rupture and cell lysis (MACHLIN;BANDICH, 1987). One of the first implications of aggression to the blood vessels is the oxidative modification of low-density lipoprotein (LDLc), which can promote the development of atherosclerosis from the endothelial dysfunction with subsequent formation of foam cells and complex plaques composed of necrotic cellular debris, lipid and fibrous tissue (TINKEL et al, 2012).…”

“…The quantification of the protein was performed following the Lowry method (LOWRY et al, 1951), where the maximum absorbance for the solution of FolinCiocalteau, because of its interaction to the albumin protein of the bovine serum, occurs at 625 ηm.…”

The 18 kDa Translocator Protein and Atherosclerosis in Mice Lacking Apolipoprotein E

“…Induction of vascular cell adhesion molecule-1 (VCAM-1), a member of the immunoglobulin superfamily of CAMs, is increasingly described as the key factor in monocyte infiltration (Nakashima et al, 1998;Truskey et al, 1999). ApoE-knockout mice (apoE KO) have been extensively used to study the relation of hypercholesterolemia and lipoprotein oxidation to atherogenesis Yang et al, 2009;Kunitomo et al, 2009). ApoE-deficient mice have elevated VCAM-1 in aortic lesions (Nakashima et al, 1998), which enhances monocyte recruitment and adhesion (Ramos & Partridge, 2005), while apoE expression in the artery wall reduces early foam cell lesion formation (Hasty et al, 1999).…”

“…These and other findings suggest that inflammation is a primary process for atherosclerosis (Ziccardi et al, 2002;RodriguezMoran et al, 2003). Although high dietary intake of the anti-oxidant vitamin E and C has been associated with reduced risk of cardiovascular disease (CVD), well powered clinical trials in atherosclerosis-related CVD have indicated that supplements with vitamin C or vitamin E alone do not provide sufficient benefit, in comparison to, for example, statins (Kunitomo et al, 2009). Furthermore, specific antioxidants scavenge or metabolize some, but not all of the relevant oxidized molecules (Stocker and Keaney, 2004).…”