Let's talk a bit about modified LDLs which is a major cause of endothelial injury. Former heart surgeon Dr Lundell emphasized two processes that modify LDLs -- oxidation & glycation. I extracted some important facts regarding oxidized LDL from "Big Fat Surprise" & share with you: Vegetable oils (eg. soybean oil, corn oil, canola oil) oxidize easily, and heat speeds up the reaction, especially when heated for hours, as in restaurant fryers. Linoleic acid (omega-6 PUFA) comprises 50.3% of soybean oil, 53.5% of corn oil, 51.5% of cotton seed oil, 65.7% of sunflower oil and it degrades into oxidation products such as free radicals, degraded triglycerides, and others. One of the oxidation products of a range of vegetable oils, called 4-hydroxynonenal (HNE) could be produced at temperatures well below those regularly used for frying and long before the oils start to smoke or smell. HNE is one of those aldehydes which are extremely chemically reactive, causing rapid cell death, interfering with DNA and RNA, and disturbing basic cell functioning. Aldehydes also cause oxidative stress to every possible kind of tissue, with a great diversity of deleterious effects to health, all of which are likely to occur at levels normally consumed by humans. HNEs cause LDL-C to oxidize, which is an important step in the atherogenic process. The oxidative modification hypothesis proposes that oxidized LDL had the potential to cause foam cell formation.
Another important topic is glycation of LDL which is common in diabetic patients. Substances, termed advanced glycosylation endproducts (AGE), accumulate in diabetic tissues, may be toxic, and may lead to the cellular alterations associated with atherogenesis. Furthermore, AGEs are chemotactic for human monocytes in vitro and could play a role in atherogenesis as vascular connective tissue matrix wil accumulate AGEs with time. The presence of the AGEs in the lesions of atherosclerosis seems well established.
Myocardial infarctions occur as a result of erosion or uneven thinning & rupture of the fibrous cap, often at the shoulders of the lesion where apoptosis may occur. Stable advanced lesions usually have uniformly dense fibrous caps. The potentially dangerous lesions are often nonocclusive & thus difficult to diagnose by angiography, yet at autopsy active inflammation is evident in the accumulation of macrophages at sites of plaque rupture. Plaque rupture & thrombosis may be responsible for as many as 50% of cases of acute coronary syndromes & myocardial infarction.
In conclusion, Ross said atherosclerosis is clearly an inflammatory disease & does not result simply from accumulation of lipids. If we can selectively modify the harmful components of infammation in the arteries & leave the protective aspects intact, we may create new avenues for the diagnosis & management of disease in the 50% of patients with CVD who do not have hypercholesterolemia.