AA Oxidopathy References


Majid Ali, M.D.

Redox regulation in the circulating blood is a dynamic, elaborately integrated complex of diverse energetic-molecular events that involve all plasma and cellular oxidant-antioxidant systems. Changes of redox dysregulation in circulating blood comprise cell erythrocyte membrane damage and cell lysis, zones of plasma congealing, activation of polymorphonuclear leukocytes and monocytes, transformation of monocytes into macrophages, and formation of microclots and microplaques. We designate this broad spectrum of changes as AA oxidopathy. Derangements of the clotting-unclotting equilibrium (CUE), involving both established and as yet unrecognized coagulation pathways, are designated oxidative coagulopathy. Spontaneity of oxidation in the circulating blood assures that oxidative coagulopathy, and fibrinolytic response triggered by it, occurs in health at all times. Oxidatively triggered molecular responses to AA oxidopathy occurring in the endothelial cells, myocytes, and fibroblasts that constitute atherogenesis are regarded as consequences of unrelenting AA oxidopathy.
Plasma cholesterol, a weak antioxidant, initially prevents AA oxidopathy—albeit inadequately—and, once oxidized, feeds the oxidative fires set off by a host of oxidative stressors discussed above. Chronic use of HMG Co-reductase inhibitor statin drugs provides minimal short-term clinical benefits and, as yet undefined, long-term chemical consequences of disruption of lipid metabolism and carcinogenicity. The short-term benefits of statin drugs, in our view, may be largely attributed to their ability to address the single issue of mycotoxicity in the pathogenesis of oxidative coagulopathy.
The AA oxidopathy hypothesis provides a rational explanation of atherogenic mechanisms of risk factors of IHD as well as for the coronary vasospastic events that cause clinical ischemic heart disease without coronary occlusive disease. The proposed hypothesis also calls for a radically different clinical approach to prevention and reversal of ischemic heart disease. Specifically, it requires an integrative approach that addresses all of the following principal categories of chronic oxidant stressors: 1) adrenergic hypervigilence; 2) glucose-insulin dysregulation; 3) fungal and bacterial stress proteins, as well as other types of toxins; and 4) ecologic oxidants. The dominant prevailing approaches to ischemic coronary artery disease—such as angioplasty, coronary bypass and multiple drug therapies that focus on calcium channel and adrenergic blockade—evidently do not address any of the causes of AA oxidopathy, and thus cannot be regarded as optimal therapies.


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