Cigarette smoke and LDL cooperate in reducing nitric oxide bioavailability in endothelial cells via effects on both eNOS and NADPH oxidase.

The ubiquitous free radical nitric oxide (NO) plays an important role in many biological processes, including the regulation of both vascular tone and inflammatory response; however, its role in the effects of cigarette smoke exposure on atherosclerosis remains unclear. Our aim was to study the mechanisms of NO regulation in endothelial cells in response to cigarette smoke exposure in vitro. Using human umbilical vein endothelial cells (HUVEC), we have demonstrated that combining non-toxic concentrations of cigarette smoke bubbled through PBS (smoke-bubbled PBS [sbPBS]) with native LDL (nLDL) significantly reduces the amount of bioavailable NO.

Cigarette smoke enhances abdominal aortic aneurysm formation in angiotensin II-treated apolipoprotein E-deficient mice.

Cigarette smoke, hyperlipidemia, and hypertension with the risk of development and progression of atherosclerosis and associated pathologies such as abdominal aortic aneurysm (AAA) are correlated. We examined the interaction of cigarette mainstream smoke (MS) and angiotensin-II (Ang II)-induced hypertension in the atherosclerotic process using hyperlipidemic apolipoprotein E-knockout (ApoE(-/-)) mice. ApoE(-/-) mice were treated with Ang II for 4 weeks and then further exposed to MS or to fresh air for 4 weeks.

Progression of atherosclerosis in the Apo E-/- model: 12-month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet.

This study was performed to gain information about the influence of two cardiovascular risk factors, cigarette mainstream smoke (MS) and high-cholesterol/fat diet, on the progression of atherosclerosis in apolipoprotein E-deficient (Apo E-/-) mice. Eight to 12-week-old mice were whole-body exposed for up to 12 months (6h/day, 5 days/week) to diluted cigarette mainstream smoke at total particulate matter (TPM) concentrations of 100 or 200mg/m(3), or to filtered fresh air (sham) in combination with a normal chow diet or a high-cholesterol/fat diet. Cholesterol in the aortic arch was elevated in the high-cholesterol/fat diet groups exposed to 200 mg TPM/m(3) compared to sham at all time points.

Cigarette smoke exposure promotes arterial thrombosis and vessel remodeling after vascular injury in apolipoprotein E-deficient mice.

Background: Cigarette smoking is a major risk factor for the development of cardiovascular disease. However, in terms of the vessel wall, the underlying pathomechanisms of cigarette smoking are incompletely understood, partly due to a lack of adequate in vivo models.

Methods: Apolipoprotein E-deficient mice were exposed to filtered air (sham) or to cigarette mainstream smoke at a total particulate matter (TPM) concentration of 600 microg/l for 1, 2, 3, or 4 h, for 5 days/week.

Animal models of hypertension.

Hypertension affects approximately 25% of adults and is a major risk factor for cardiovascular disease. Although there are currently adequate therapeutic options for humans with hypertension, the molecular mechanisms underlying hypertension are still relatively unknown. The generation of hypertensive animal models provides an excellent modality to not only study the pathophysiology but also test innovative therapeutics.