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Am J Pathol. 1977 Mar; 86(3): 675–684.
PMCID: PMC2032127

Response to injury and atherogenesis.


We postulate that the lesions of atherosclerosis arise as a result of some form of "injury" to arterial endothelium. This injury somehow results in alteration in endothelial cell-cell attachment or endothelial cell-connective tissue attachment, so that forces such as those derived from the shear in the flow of blood result in focal desquamation of endothelium. This is followed by adherence, aggregation, and release of platelets at the sites of focal injury. During the process of release, a mitogenic factor is secreted from the platelets which, together with plasma constituents, gains entry into the artery wall, resulting in focal intimal proliferation of smooth muscle cells. This intimal proliferation is accompanied by the synthesis of new connective tissue matrix proteins and often by the deposition of intracellular and extracellular lipids. Studies in cell culture of arterial smooth muscle have demonstrated that the principle mitogen present in blood serum is a platelet-derived factor that is present in all whole blood sera and missing in serum derived from platelet-free plasma. In the absence of the platelet factor, smooth muscle cells are quiescent in culture. This platelet mitogen is also active in vivo, since experimentally produced lesion of atherosclerosis induced mechanically by diet or by homocystine can be prevented if platelets are missing, as in thrombocytopenia, or if platelet function is impaired as a result of the use of platelet inhibitors such as dipyridamole. These studies point to the key role of the platelet in the stimulation of intimal smooth muscle proliferation that leads to the development of lesions of atherosclerosis.

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Selected References

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