Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or interferon-gamma receptors result in reduced les...

BACKGROUND The endothelial isoform of nitric oxide synthase (eNOS) has been considered to exert an antiatherosclerotic role through synthesis of NO. However, eNOS has been shown to generate superoxide, which could oxidize LDL and promote atherosclerosis. We sought to determine the role of eNOS in diet-induced fatty streak formation through the use of eNOS-deficient mice. METHODS AND RESULTS M...

OBJECTIVE Whereas estradiol prevents fatty streak deposit in immunocompetent apoE-/- or LDLr-/- mice, it is totally ineffective in immunodeficient mice, underlining the key role of immunoinflammation in this effect. In the present work, the role of several major pro- and antiinflammatory cytokines involved in the atheromatous process was evaluated in the effect of estradiol on fatty streak cons...

Epidemiological studies and animal trials have suggested that dietary antioxidants protect against atherosclerosis. To test this hypothesis, C57BL/6 mice were fed atherogenic diets supplemented with either vitamin E or butylated hydroxytoluene (BHT). Three groups of 20 mice were fed for 15 weeks on diets containing 1% cholesterol and 0.5% cholic acid. The diet of two groups was supplemented wit...

Morphologic and immunocytochemical studies were conducted to determine the sequence of cellular interactions that occur during the initiation of the fatty streak in the aorta of Watanabe Heritable Hyperlipemic rabbits and comparably hypercholesterolemic fat-fed rabbits. Watanabe rabbits from 3.5 weeks gestation to 2 months of age and fat-fed rabbits from 1 week to 2 months duration of hyperchol...

Estrogen Replacement Therapy (ERT) in postmenopausal women may decrease the risk of Coronary Artery Diseases (CAD). We hypothesized that Nitric Oxide (NO) releasing due to ERT may be the essential factor by which endothelial permeability decreases. Four groups of ovariectomized rabbits were under investigation for five weeks. Groups 1 & 4 received high cholesterol diet and other two groups (2 &...

The ASCI is notable for two unique functions--the annual meeting and The Journal of Clinical Investigation. Both have inspired us over the 37 years of our collaborative adventures in research. In this retrospective, we review highlights from our 26 joint papers in the JCI, focusing on two papers that revealed the consequences of lipid accumulation with implications for atherosclerosis and steat...

Maternal hypercholesterolemia during pregnancy is associated with a marked increase in aortic fatty streak formation in human fetuses and faster progression of atherosclerosis during normocholesterolemic childhood. However, the mechanisms responsible are unknown, and the contribution of genetic differences is difficult to assess in humans. The goal of this study was to determine whether materna...

The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two different types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. Lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) as well as its (R)-enantiomer at 3 mg kg(-1) week(-1) were given by subcutaneous injection for 10 weeks to White New Zealand rabb...

Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) play an important role during the development of atherosclerosis. 3-Deazaadenosine (c(3)Ado), an adenosine analogue, inhibits endothelial-leukocyte adhesion and ICAM-1-expression in vitro. We hypothesized that c(3)Ado is able to prevent the expression of adhesion molecules and at...