Infiltration of monocytes into the arterial wall is an early cellular event in atherogenesis. Recent evidence shows that C-reactive protein (CRP) is deposited in the arterial intima at sites of atherogenesis. In this study, we demonstrate that CRP deposition precedes the appearance of monocytes in early atherosclerotic lesions. CRP is chemotactic for freshly isolated human blood monocytes. A sp...

Pak1 plays an important role in various cellular processes, including cell motility, polarity, survival and proliferation. To date, its role in atherogenesis has not been explored. Here we report the effect of Pak1 on atherogenesis using atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice as a model. Disruption of Pak1 in ApoE(-/-) mice results in reduced plaque burden, significan...

A critical role for hypercholesterolemia in the pathogenesis of atherosclerosis is firmly established. However, we still have much to learn about how hypercholesterolemia leads to the development of atherosclerotic heart disease and the spectrum of cellular participants involved. Atherosclerosis is viewed as a chronic inflammatory process, with our focus of attention dwelling on the role of cel...

The term ‘atherosclerosis’ is generally employed for a disease process characterized by the formation of atheromas (fibrofatty intimal plaques) resulting in progressive hardening of the arterial wall, loss of vascular elasticity, and luminal compromise. Different segments of the vascular tree vary in their susceptibility to develop atherosclerotic lesions: atheromas have been described characte...

This symposium on mechanisms in the development of early atheroma was held at the Ciba Foundation in London, July 5-6, 1972. For American students of atherosclerosis it differs both in the composition of the panel and in the selection of areas discussed. Only three of the 22 participants are from the United States. Eleven are from the United Kingdom, three from elsewhere in Europe, three from I...

The anoxemia theory proposes that an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerosis. There is now substantial evidence that there are regions within the atherosclerotic plaque in which profound hypoxia exists; this may fundamentally change the function, metabolism, and responses of many of the cell types found wit...

The balance between vascular oxygen supply and metabolic demand for oxygen within the vasculature is normally tightly regulated. An imbalance leads to hypoxia and a consequential cascade of cellular signals that attempt to offset the effects of hypoxia. Hypoxia is invariably associated with atherosclerosis, wound repair, inflammation and vascular disease. The anoxaemia hypothesis proposes that ...

Atherosclerotic lesions are initiated and progress largely as a result of a chronic, fibroproliferative, inflammatory response. This review discusses how Chlamydia pneumoniae could conceivably contribute to this chronic inflammatory response and reports on recent in vivo and in vitro studies. In vivo studies in mice demonstrate that C. pneumoniae infection is disseminated to the artery wall fol...

Atherogenesis is the pathobiological process, which underlies atherosclerotic cardiovascular disease and evolves in the 3 stages of initiation, progression, and complication to clinical significance. Of note, this process is associated with neovascularization, and it was not until recently that the implications of angiogenesis in atherogenesis were delineated. This article gives an updated over...

A bout 45 years ago George Lyman Duff, together / \ with Gardner McMillan, presented a paper J. \ . called "The Effect of Alloxan Diabetes on Experimental Cholesterol Atherosclerosis in the Rabbit" at the Second Annual Meeting of the American Society for the Study of Arteriosclerosis, and two papers describing that work were subsequently published in the Journal of Experimental Medicine in 1949...