Atherosclerosis is a particularly unpleasant age-related condition not because it causes great suffering along the way but because it is comparatively invisible right up until the point at which it kills you suddenly. In atherosclerosis the blood vessel walls are thickened by material that is largely composed of immune cells and the fatty remnants of dead cells. Eventually this material becomes unstable enough to cause major blood vessel failure or for a piece to break off and catastrophically block a blood vessel elsewhere in the body, leading to stroke or heart attack.
Once atherosclerotic plaques exist in earnest, they become a ongoing industry of inflammation, cell death, and restructuring on the inside of your blood vessels. The immune cells present in the area act to maintain inflammatory conditions that help to make things worse and attract more immune cells, creating an ever larger mess as time goes by. The starting point for this process involves cholesterols, however. Low-density lipoproteins (LDL) can become damaged by oxidative reactions and in large enough numbers their presence causes a response in blood vessel walls, wherein the tissues issue a call for immune cells to turn up and remove the unwanted damaged LDL molecules. Sometimes this all proceeds according to plan and the harmful LDL is removed, but sometimes the immune cells cannot cope with the ingestion of LDL and die. This can snowball into precursor fatty structures that will grow to become atherosclerotic plaques.
So progression of atherosclerosis is one of the many aspects of aging that can be sped by an environment of greater chronic inflammation in the body. But it is also driven by levels of damaged LDL. That second item is the link between causes of chronic oxidative stress in tissues, rising levels of oxidative molecules roaming to cause unwanted reactions and damaged proteins, and damage such as that of atherosclerosis. Damage caused to mitochondria over the course of aging in particular is thought to drive rising levels of oxidative molecules such as reactive oxygen species: some cells in every tissue become very dysfunctional as a result of this, overtaken by damaged mitochondria and turned into exporters of oxidative molecules. That flow of oxidative molecules can react with and damage important proteins such as LDL that travel far in the body via the circulatory system - and thus contribute to the roots of atherosclerosis over the years.
So I've sketched a picture here, but the reality is that these are complex mechanisms and in absence of repair technologies to remove one or another contribution to atherosclerosis it is hard to prove the degree to which various different sources contribute to the pathology of the condition. For example, there are other ways to modify LDL so as to cause pathology, but this is all the more reason to work harder on repair biotechnologies, as I see it. They are an investigative tool that compares favorably in projected cost and time at this point in comparison to the slow and painfully expensive approach of gathering a full understanding of any process in the aging of metabolism. That all said, here is an example of present research aimed at improving understanding of the causes of atherosclerosis, a paper that touches on some of those other means to alter LDL in harmful ways:
Atherosclerosis is an inflammatory process where lipids in the form of LDL cholesterol (also called 'bad cholesterol') are stored in the artery walls. The activation of the immune system in the form of T-cells, among others, plays a vital role, particularly for rupturing the atherosclerotic plaques which, the primary cause of myocardial infarction and stroke. LDL is only taken up in the artery wall after modification, a process where oxidation is one probable underlying cause. Enzymes in the artery walls can also modify LDL making it inflammatory. Most basic scientific studies in the field are based on mouse models with genetic changes as mice cannot develop arteriosclerosis or cardiovascular disease.
[The researchers] studied inflammatory and immune defence reactions in atherosclerosis and cardiovascular disease using plaque cells and blood from patients with cardiovascular disease. The researchers have observed that the lipids (phospholipids) in modified LDL appear to be one of the primary causes. The research team has shown that LDL that is modified by enzymes in the artery walls can activate dendritic cells, which in turn play a key role in activating the T-cells. Non-modified, regular LDL on the other hand had no effect on these cells in the study. The research also indicates the possible existence of a mechanism, namely that stress proteins (also called heat shock proteins) are expressed, which is decisive when modified LDL activates the dendritic cells and T-cells. The study shows that a plasma protein Annexin A5 decreases inflammation and modulates immune reactions to modified LDL, which creates a protective effect.
Atherosclerosis is an inflammatory disease, where activated immunocompetent cells, including dendritic cells (DCs) and T cells are abundant in plaques. Low-density lipoprotein modified either by oxidation or by human group X-secreted phospholipase A2 (LDLx) and heat shock proteins (HSP), especially HSP60 and 90, have been implicated in atherosclerosis.
We previously reported that Annexin A5 inhibits inflammatory effects of phospholipids, decreases vascular inflammation and improves vascular function in apolipoprotein E−/− mice. Here, we focus on the LDLx effects on human DCs and T cells. Our data show that modified forms of LDL such as LDLx but not native LDL activate human T cells through DCs. HSP60 or 90 contribute to such T-cell activation. Annexin A5 promotes induction of regulatory T cells and is potentially interesting as a therapeutic agent.
You can clearly see the standard research approach here: look for ways to interfere in the details of the process of development (tinker with levels of Annexin A5 to try to reduce the inflammation levels caused by the presence of damaged molecules) rather than address the root cause (the presence of that damaged LDL in the first place). When you work from the end state backwards, points at which the process might be altered are the first things to be discovered. That doesn't mean it is a good approach, however. What it means is that it is the approach most likely to win further funding and a prospect of entering the drug development and regulatory pipeline as they are presently instantiated. Effectiveness of the research strategy as a whole is a much lower priority, sad to say.