Vanderbilt University Researchers Find a New Approach to Atherosclerosis Treatment

Atherosclerosis is a type of vascular disease characterized by the narrowing of arteries due to plaque buildup. This buildup of fatty substances clogs the arteries and can result in serious consequences in the form of coronary artery disease, peripheral artery disease, and angina among others. Furthermore, if the clogged artery supplies the heart or the brain, narrowing or blockage of it can cause a heart attack or stroke respectively.

Atherosclerosis

Atherosclerosis

Atherosclerosis is an inflammatory, slow, and progressive disease that begins early on in life but does not cause any detrimental health effects until later on in life. Low levels of high-density lipoprotein (HDL) or the good cholesterol and high levels of low and very-low-density lipoproteins (LDL, VLDL) or bad cholesterol increase the risk of atherosclerosis significantly.

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Oxidative stress causes oxidative modification of the lipoproteins and this plays a critical role in the development of atherosclerosis. The oxidation results in the formation of foam cells which initiate the buildup in arteries and the oxidized LDL induces inflammation, and cellular toxicity.

Use of statins or anti-cholesterol medications especially the LDL-lowering drugs helps reduce the risk of heart attack, stroke, and other consequences associated with atherosclerosis. However, they have no effect on the inflammatory risk associated with atherosclerosis, which requires a totally new therapeutic approach.

A new Vanderbilt Study

A research study published in Nature Communications journal by the authors Huan Tao and Jiansheng Huang of the Vanderbilt University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, and Atherosclerosis Research Unit along with their team claims to have found a scavenger molecule that may help reduce the inflammatory risks of atherosclerosis.

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The scavenger molecule, 2-HOBA is designed to attack the highly reactive dicarbonyls that play an important role during the lipid peroxidation seen with oxidative stress. These dicarbonyls attach to DNA, proteins, and phospholipids causing a cellular alteration that can result in inflammatory responses similar to those seen in atherosclerosis.

Method of study

For this study, Tao and his team treated animal models of LDL receptor negative female mice suffering from familial hypercholesterolemia with 2-HOBA. The mice were divided into three groups based on different treatment models and all were fed a western-type diet for 16 weeks.

Results of the study

Tao and his team found that the mice treated with 2-HOBA rather than vehicle (water) or 4-HOBA had significantly reduced atherosclerosis without impacting the triglycerides and the cholesterol levels. In addition to that, 2-HOBA was found to decrease cell death resulting in highly stable atherosclerotic plaques, reducing the risk of plaque rupture. 

The research team is now planning a clinical trial to apply their study findings and evaluate the efficiency of 2-HOBA in reducing oxidation of HDL and LDL.

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Reference

Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr−/− mice

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