Atherosclerosis, Cancer, Wound Healing, and Inflammation - Shared or Parallel Evolution

Abstract

Wound healing is a complex process involving inflammatory cell activation and invasion as well as scar tissue deposition (in the form of fibrotic tissue and collagen matrix). With tissue repair there is active cell proliferation designed to heal the damaged tissues. Recent work has suggested that cancer is a form of dysregulated wound healing where inflammatory responses and cellular proliferation goes awry. Additionally other diseases such as the highly prevalent atherosclerotic coronary plaque are hypothesized to be a form of unregulated wound healing. The ‘Response to Injury’ hypothesis was first presented by Russell Ross as an explanation for atherosclerosis. The basic premise for this theory on the etiology of atherosclerotic arterial disease is that all forms of damage to the arterial wall, whether hypertension, hyperlipidemia, angioplasty injury or transplantation, cause an accelerated injury response with aggressive inflammatory cell responses and cell proliferation, in short an unchecked form of wound healing. Prior to Dr Ross’ theory, Earl Benditt postulated that human atheromata were benign intimal tumors. He demonstrated that many atherosclerotic plaques were derived from individual smooth muscle cells using X chromosome inactivation patterns with results that were highly suggestive of a proliferating monoclonal tumour cell. More recent work has now linked excess inflammation with growth and instability of atherosclerotic plaque and with progression of invasive cancers. There are thus now many parallels in developing cancer and atherosclerosis and many close associations between cancer, atheroma and wound healing. These findings raise one basic question – Are carcinogenesis and atherogenesis manifestations of the same initiating disease generating events or simply parallel manifestations of similar pathogenic disease mechanisms, e.g. are these shared or parallel evolutions. The history of our understanding of the pathogenesis of wound healing and inflammation helps in understanding these disorders and the underlying mechanisms of disease. Ilya Ilyich Mechnikov (18451916), a Russian biologist and zoologist who moved to work at the Institute Pasteur in Paris, was the first to discover the existence of innate immunity, also termed inflammation. Although the innate immune system is now known to cure the majority of infections and drives wound healing after injury long before the adaptive immune response becomes active, Mechnikov’s initial discovery of this more ancient defense system was viewed with some suspicion and he shared