Virchow observed that deposits of lipids were secondary to an initial inflammation characterized by injury-type changes in the endothelial surface of the arterial lumen. There was an initial gelatinous swelling under the intima with distinctive inflammation-type cells which proceeded to the formation of the complex atherosclerotic plaque with lipid deposition, central necrosis and encasing fibrosis. Virchow was expert in matters of inflammation and was the first to use the term granuloma in describing the pathological features of diseases such as tuberculosis and syphilis. Interestingly, cellular features of the atherosclerotic lesion are now recognized as those of delayed hypersensitivity, the cardinal manifestation of which is granuloma.
A number of subsequent studies supported the inflammation findings of Virchow. In 1903, Sumikawa produced arterial intimal proliferation by bacterial injections. In 1903, and again in 1908, Thorel reported the high frequency of atherosclerotic lesions in children dying of infectious diseases. Jores (1927) reported similar findings in such autopsies and stressed his observation that fatty deposits were not the primary finding.
Saltykow (1908) induced human-like atherosclerosis lesions by injecting cultures of staphylococci and the administration of alcohol (alcohol is a fungal toxin (mycotoxin) produced by Saccharomyces cerversiae). A highly significant feature of his induced animal atherosclerosis lesions was large fatty masses within the thickened areas of the intima. His studies were accepted at the time as proof of a "toxico-infectious" etiology of atherosclerosis.
Karsner and Bayles (29) reported that infectious processes may be the forerunner of coronary atherosclerosis. Kling (1933) described the "infectious-toxic" etiology of atherosclerosis.
Spodick (1985) reported that 42 of 150 patients admitted with acute myocardial infarction had experienced acute respiratory symptoms during the two weeks prior to admission.
Steinberg and Witztum (1990), point out that there is increasing movement away from viewing atherosclerosis as a primary lipid/metabolic process and towards an attempt to find a nonlipid cause for the cellular reactions which are present in the arterial wall and which appear to attract immnoresponsive cells from the circulation.
When one reviews these cells in the light of the rapidly expanding body of knowledge relative to the highly specific roles that various cells play in inflammation, particularly in immunologic terms, there is no longer any doubt that Virchow had been right in the first place; atherosclerosis is an inflammatory disease typical of microbial-induced diseases.
The Microbial Granulomatous Nature Of Atherosclerotic Inflammation.
The cellular and humoral findings in atherosclerotic lesions are now recognized as typical of delayed hypersensitivity.
The characteristic manifestation of delayed hypersensitivity is the
immunological granuloma which is defined by Turk and Parker (1983) as a
granuloma associated with epithelioid cell formation and activation of
fibroblasts resulting in marked fibrosis. Atherosclerotic plaques fall
within definition. Such granulomas are typically caused by the more complex
microbes such as Mycobacterium and Fungi. Neither viruses nor simple bacteria
cause immunological granulomas.