Author(s): Rakhshinda Zafar
Based on my clinical experience and knowledge gained through extensive research in this area, I have come up with a hypothesis which sheds more light in the pathogenesis of cardiovascular diseases. Atherosclerosis is implicated as playing the key role in the pathogenesis of cardiovascular diseases which involves large and medium sized arteries. There is now evidence that atherosclerosis is an immuno-inflammatory process. My hypothesis is that chronic psychosocial stress is the main trigger for the systemic inflammation which results by activation of Hypothalamus-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medulla (SAM) axis. This stress response sets into motion innate immune response, initiating a cascade of events which include: Release of neuro-endocrine transmitters, endothelial dysfunction, and increased permeability of micro vascular circulation and increased delivery of free fatty acids in circulation among others. Liver responds by increased Low Density Lipoproteins (LDL) production which continuously enters the arteries, excess LDL is transformed into oxidized low density lipoproteins (ox LDL). ox LDL goes through pattern recognition and is recognized as antigen. Adaptive immunity is activated. ox LDL is pro oxidant, results in inflammation, reactive oxygen species are released causing oxidative stress. This causes atherosclerosis in large and medium sized arteries and tissue damage in organs sub served by micro vasculature. Hence the process being systemic inflammation is not limited to large and medium sized arteries but is global in reach involving the entire vasculature. The pathogenesis of these disorders may be classified as “stress induced, lipid mediated vascular inflammation".
This article will review stress and pathophysiology of stress, pathophysiology of cardiovascular diseases which includes endothelial dysfunction, pathogenesis of atherosclerosis, inflammation in atherosclerosis, and current concepts of diseases comprising cardiovascular diseases, including the risk factors for CVDs. It enters the stage of hypothesis based on the knowledge gained. It discusses microcirculation, and goes over disorders involving microcirculation. Oxidative Stress is reviewed followed by a brief summary. It winds up with discussion, management and conclusion.
