Multiple injurious stimuli to the endothelium, intima, media, and adventitia The endothelial cell is exposed to multiple injurious stimuli consisting of: modified LDL-cholesterol, various infection insults (viral and bacterial), angiotensin II, hemodynamic stress, LPa, glucose, homocysteine, and intimal redox stress or reactive oxygen species. As discussed in this review, the toxicity of homocysteine may act alone as well as in concert with the other multiple injurious stimuli to injure the endothelium resulting in endothelial cell dysfunction. Especially in the MS, PD, overt T2DM, and atheroscleropathy. It is of importance to note that native LDL-cholesterol is not atherogenic to the vascular intima. The process of oxidation, glycation, glycoxidation, or homocysteinylation must modify LDL-cholesterol in order to become atherogenic. Thus, the importance of the multiple injurious stimuli acting alone and synergistically to modify LDL-cholesterol and accelerate angiogenesis as seen in the accelerated atherosclerosis associated with MS, PD, and overt T2DM termed atheroscleropathy.