Coronary Artery Disease: Cholesterol and Lipids

Author: Endonita Hajzeraj

Cholesterol and Lipids

Plaque Buildup Artery Wall

Traditionally, we associate coronary artery disease with cholesterol. That plaque is caused by a buildup of cholesterol in the arteries. High cholesterol can be caused by many different factors. These factors include family history, diet and lifestyle, smoking, lack of exercise, diabetes and many more. All these factors can contribute to plaque buildup and normally, buildup is the aggregation of Low-density lipoprotein (LDL). Cholesterol is fatty and doesn’t mix well with blood, due to its hydrophobic nature, so it travels in our blood via a protein “wrapper” known as the lipoprotein (1). This lipoprotein aggregation is the beginning of the damage to your heart. To connect with the molecular basis of CAD, there is a copious amount of evidence to support the role of oxidative modification in mediating the plaque causing LDL Low density lipoprotein is Low-density lipoprotein is an independent risk factor for coronary artery disease and is associated with increased cardiovascular events (1). Low-density lipoprotein is colloquially known as “bad cholesterol” because it takes cholesterol to you arteries where it may collect in artery walls. Too much cholesterol in your arteries will lead to a buildup of plaque and this buildup causes oxidative stress on cells.

Cholesterol has a bad reputation, because of its connection to coronary artery disease. Cholesterol, however, is naturally produced in our bodies and is found in every cell in the body (2). Cholesterol is used to make vitamin D, hormones, including testosterone and estrogen, and fat-dissolving bile acids. It is extremely important, so much so that your liver makes 80% of the cholesterol to stay healthy, while the other 20% comes from the food we eat. It is used to maintain membrane potential and without it, we would not survive. That being said, cholesterol is pretty important, but too much of it can be bad.

Little is known about the contribution of high-density lipoproteins in cardiovascular health. A study conducted by Po-Chao Hsu et al determined the influence of high-density lipoprotein cholesterol on coronary collateral formation in a population with coronary artery disease. Coronary collateral circulation plays an important role in protecting myocardium, the muscular tissue in the heart, from reducing cardiovascular events (2). The development of coronary collaterals is an adaptive response to protect the heart and serves as a conduit bridging the coronary vessels. Collateral circulation can protect and preserve myocardium from ischemia, which is an inadequate blood supply to the heart or other vital organs (2). HDL has been reported to have anti-atherogenic, anti-inflammatory, and antioxidant properties in the literature. HDL enters the blood on its own, but it then picks up cholesterol to become HDL cholesterol. The previous hypothesis as to how HDL helped the heart was that it acted as a garbage collector that picked up cholesterol from artery walls and delivered it to the liver for disposal (3). While that still holds true, HDL can help in other ways. If enough HDL is available, it will latch on to the artery wall and carry it to the liver to be disposed of. This is called reverse transport, since the cholesterol is returned back to where it was originally manufactured. As mentioned above, because oxidized cholesterol is the plaque that causes arterial damage, HDL shows that it has antioxidant activity that protect LDL cholesterol from free radicals (3). The inflammation does not simply come from e mechanical buildup of cholesterol, but it also stems from the oxidized cholesterol and perpetuated white blood cells, T lymphocytes and macrophages, and elevated levels of C-reactive protein (3). HDL helps decrease the inflammation and neutralizes C-reactive protein’s tendency to perpetuate the inflammatory cycle (3).

In a study conducted by Xiao-min et al, they looked at Preβ1-high-density lipoprotein, as a minor HDL, that enters the plasma as a substrate or product in interconversion of HDL species (4). The fasting preβ1-HDL concentration has been reported elevated in patients with coronary artery disease, and so the authors needed to further investigate the role of preβ1-HDL and CAD. Preβ1-HDL is recognized as the primary acceptors of cholesterol effluxes by the dominant ATP-binding cassette A1 transporter in arterial macrophages, which is a critical step in reverse cholesterol transport. Once the cholesterol is esterified with a free fatty acid, cholesterol esters are then incorporated into cores of α-HDL. This is then transferee from α-HDL into cores of acceptor lipoproteins by cholesterol ester transfer protein (4). Cholesterol ester transfer protein is one of the decisive factors that determines HDL cholesterol, mediates the transfer of cholesteryl esters from HDL to LDL, which increases plaque buildup (4). This study determined that preβ1-HDL can be used as a biomarker for the development and severity of CAD, although the authors did mention that the relationship is still controversial.

The role of cholesterol in the presence of coronary artery disease might arguably be one of the largest pieces of the puzzle. While we need the production of cholesterol to survive, it can also have dire consequences. The balance between HDL and LDL is what can help us from building plaque in our arteries and causing coronary artery disease.

Citations:

  1. 1. Supriya Simon and T. Vijayakumar Indian J Clin Biochem. 2013 Jul; 28(3): 215–226. Published online 2013 Feb 12. doi:  10.1007/s12291-013-0303-6

2. Hsu, Po-Chao, Ho-Ming Su, Suh-Hang Juo, Hsueh-Wei Yen, Wen-Chol Voon, Wen-Ter Lai, Sheng-Hsiung Sheu, and Tsung-Hsien Lin. 2013. “Influence of High-Density Lipoprotein Cholesterol on Coronary Collateral Formation in a Population with Significant Coronary Artery Disease.” BMC Research Notes 6 (1): 1–5. https://doi.org/10.1186/1756-0500-6-105.

3. Park, Hyun Woong, Wan Ho Kim, Ki-Hong Kim, Dong Ju Yang, Ji Hye Kim, In Girl Song, Taek-Geun Kwon, and Jang-Ho Bae. 2013. “Carotid Plaque Is Associated with Increased Cardiac Mortality in Patients with Coronary Artery Disease.” International Journal of Cardiology 166 (3): 658–63. https://doi.org/10.1016/j.ijcard.2011.11.084.

4. Xiao-min Bu, Dong-mei Niu, Jia Wu, Yun-long Yuan, Jia-xi Song, and Jun-jun Wang. 2017. “Elevated Levels of Preβ1-High-Density Lipoprotein Are Associated with Cholesterol Ester Transfer Protein, the Presence and Severity of Coronary Artery Disease.” Lipids in Health & Disease 16 (January): 1–7. https://doi.org/10.1186/s12944-016-0394-1.

 

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