Coronary Artery Disease- Molecular basis of CAD

Author: Endonita Hajzeraj

Molecular Basis of Coronary Artery Diseasehttps://www.google.com/search?q=oxidative+stress+coronary+artery+disease&source=lnms&tbm=isch&sa=X&ved=0ahUKEwj4w4zws73aAhXkp1kKHQy5D-sQ_AUICigB&biw=844&bih=774#imgrc=aq7yJ_PhCglgYM:

Oxidative Stress and Risk factorsIt is unlikely that we have gone through our lives without hearing or knowing about coronary artery disease (CAD). According to the CDC, nearly one in every four deaths that occur in the United States every year are due to coronary artery disease (1). This disease is the leading cause of deaths for both men and woman and yet, the public is still not completely informed about CAD.  The extent of information that people receive about CAD is that it is caused by a buildup of plaque in the arteries, which causes narrowing of the arteries, reducing blood flow, and causing other effects such as heart attacks. While this information is true, there are many pieces of the CAD puzzle that are missing, and this is the place to help put those pieces together.

There are many pieces of the CAD puzzle. Coronary artery disease can be caused by many factors, and these factors all fit together in that puzzle. Proteins play a colossal role in normal functioning of chemical processes, and sometimes variations to certain proteins can lead to diseases. Under normal conditions, there is oxidative stress in normal chemical processes that produce reactive oxygen species. Amino acids, peptides, and proteins are then vulnerable to attack by a variety of the free radicals (2). Sometimes, cells are not able to overcome oxidative stress and they become damaged and die. Damaged cells can cause harm and thus further progress the beginning of a disease. The increase in the generation of reactive oxygen species seems to be due to the impaired mitochondrial reduction of molecular oxygen, secretion of reactive oxygen species by white blood cells, as well as radiation or air pollution (2). Physiologically, ROS produce changes in subcellular organelles, and induce intracellular Ca=2 overload that can compromise the integrity of the cell. A study conducted by Kaneda et al. progresses from previous research that reported advanced oxidation protein products (AOPP) in the plasma of uremic patients. To build on this research, Kaneda et al. wanted to examine the association between plasma AOPP levels and coronary artery disease. They determined, through multivariable models, that plasma AOPP levels were significantly related to coronary artery disease status (2). This study suggests the link between AOPP and coronary artery disease. From this data, we can say that oxidative stress plays a role in the events of heart injuries. Oxidative stress can cause these proteins to become damaged and thus hinder their abilities to protect against diseased states.

One of the main contributing factors that causes coronary artery disease is atherosclerotic plaque development in the walls of coronary arteries. This plaque buildup is associated with an aggregation of cholesterol. A healthy heart will try to get rid of the plaque by sending in white blood cells to trap the cholesterol. This, in turn, causes inflammation, which triggers muscle cells in the artery wall to multiply and form a cap over the area (3). The constant proliferation of vascular smooth muscle cells promotes plaque formation, whereas apoptosis of vascular smooth muscle cells promote the inflammation. The work of Lai et al. progresses on previous reports that microRNAs are potential diagnostic biomarkers in cardiovascular disease, especially in CAD. They determined that in patients with CAD, microRNA-574-5p expression was significantly increased and had a proportional relationship with the severity of the disease (4). To test the relationship, the authors overexpressed microRNA-574-5P and they determined that it promoted cell proliferation and inhibited apoptosis in vascular smooth muscle cells. The study promotes the idea that microRNA-574-5p is a CAD related factor and that it may serve as a potential molecular target for CAD treatment (4). People colloquially refer to heart disease as the “silent killer” meaning, many people do not know they have plaque buildup in their arteries or coronary artery disease, until a cardiovascular event occurs. Finding out at this time might just be a little too late. We learned that microRNAs might help us independently predict future cardiovascular events, but there is another protein that can help with that problem too. The inflammation that occurs is part of cell death of these vascular cells and also the plaque rupture within the arteries. The strong evidence suggests that coronary artery disease and other cardiovascular conditions are linked to inflammation. High-sensitivity C-reactive protein (hsCRP) might just be another independent. The relationship of high sensitivity C-reactive protein with presence and severity of coronary artery disease was evaluated by Rashid et al. Using Gensini scoring or vessel scoring, the authors observed that hsCRP is a marker of the presence and severity of CAD (5). This can be explained as that hsCRP is an acute-phase reactant protein marker that can demonstrate inflammatory states and is advantageous in that it can be measured at any time of day. The authors concluded that patients with CAD had significantly higher levels of hsCRP compared to healthy individuals (5).

As determined, proteins are important in healthy cell regulation and they are also associated with the presence of diseases, such as CAD. The severity and presence of a disease is sometimes associated with proteins function. The research of Zhu and colleagues progressed the research from previously stated reports that antibodies to mycobacterial heat shock protein 65 (HSP60) are associated with carotid artery thickening. From this research, the group examined whether human HSP60 proteins are also associated with the risk of coronary artery disease (6). Using ELISA, testing the IgG antibodies to human HSP60, the authors found that 75% of the study subject has anti-HSP60 antibodies. The results on the severity of the disease were also significant as the prevalence of HSP60 antibodies increased as the severity of the disease increased (6).  These results suggested that there is an association between the human HSP60 antibodies and both the presence and severity of CAD.

There are various proteins and their mechanisms of action that contribute to coronary artery disease and that help us understand the markers used to determine the prevalence and severity of CAD.

Citations:

  1. https://www.cdc.gov/heartdisease/coronary_ad.htm
  2. Kaneda, Hideaki, Junichi Taguchi, Ken Ogasawara, Tadanori Aizawa, and Minoru Ohno. 2002. “Increased Level of Advanced Oxidation Protein Products in Patients with Coronary Artery Disease.” Atherosclerosis 162 (1): 221–25. https://doi.org/10.1016/S0021-9150(01)00706-7.
  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. Lai, Zhongmeng, Pengtao Lin, Xianfeng Weng, Jiansheng Su, Ye Chen, Ying He, Guohua Wu, Jiebo Wang, Ying Yu, and Liangcheng Zhang. 2018. “MicroRNA-574-5p Promotes Cell Growth of Vascular Smooth Muscle Cells in the Progression of Coronary Artery Disease.” Biomedicine & Pharmacotherapy 97 (January): 162–67. https://doi.org/10.1016/j.biopha.2017.10.062.
  5. Rashid, Shahid, Muhammad Noor ul Amin, Waleed Abbassi, and Azhar Mehmood Kayani. 2017. “Association between Angiographic Severity of Coronary Artery Disease and High Sensitivity C-Reactive Protein.” Pakistan Journal of Medical Research 56 (3): 91–94. http://muhlenberg.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=125550634&login.asp&site=ehost-live&scope=site.
  6. Zhu, Jianhui, Arshed A. Quyyumi, David Rott, Gyorgy Csako, Hongsheng Wu, Julian Halcox, and Stephen E. Epstein. 2001. “Antibodies to Human Heat-Shock Protein 60 Are Associated With the Presence and Severity of Coronary Artery Disease: Evidence for an Autoimmune Component of Atherogenesis.” Circulation 103 (8): 1071–75. https://doi.org/10.1161/01.CIR.103.8.1071.
  7. https://www.google.com/search?q=oxidative+stress+coronary+artery+disease&source=lnms&tbm=isch&sa=X&ved=0ahUKEwj4w4zws73aAhXkp1kKHQy5D-sQ_AUICigB&biw=844&bih=774#imgrc=aq7yJ_PhCglgYM:

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