Importance of lipoprotein in detecting cardiovascular diseases

Cardiovascular diseases are caused by a condition known as atherosclerosis. In this, a substance called plaque builds up in the walls of arteries, making them narrow and restricting the blood flow which leads to heart attack or stroke. The plaque formation occurs due to the buildup of cholesterol in the blood vessels. This happens when the low density lipoprotein (LDL) carrying the cholesterol to the cells enters the inner lining of blood vessels and are trapped in the artery walls.

Lipoproteins play a vital role in cardiovascular diseases as a major risk factor. Specifically lipoprotein (a) which is a LDL like molecule, is a predictor of the cardiovascular diseases. Other LDL like apo B and apo A-1 are also used as biomarkers for cardiovascular diseases (Sandhu et al., 2016).

Lipoprotein as a biomarker

Lipoprotein (a) (Lp(a))  is similar to low density lipoprotein in structure with a slight difference of addition of large glycoprotein apo (a) (Weber, 1983). Studies have shown that high levels of Lp(A) levels in the plasma are associated with cardiovascular diseases (Lamon-Fava et al., 2011). The association of Lp(A) with cardiovascular diseases is due to the prothrombotic effect which occurs due to the similarity of apo(A) to the fibrinolytic pro-enzyme plasminogen. Therefore it interferes with the fibrinolytic process and thus acts as prothrombotic agent. Also, it occurs due to the fact that oxidized phospholipids preferentially binds to Lp(A) and Lp(A),  eventually deposits in the arterial walls.

Elevated levels of Lp(A) depicts the high risk of cardiovascular disease in an individual. As Lp(A) have an inhibitory role in the activation of Transforming Growth Factor (TGF).  TGF contribute to the excess growth of arterial atherosclerotic lesions caused by proliferation of smooth muscle cells and migration of these smooth muscle cells to endothelial cells (Malaguarnera et al., 2013). Lp(A) also acts as proinflammatory mediator that initiates the formation of lesions leading to atherosclerotic plaques.

Lp(A) risk factors in cardio vascular diseases

Although the levels of Lp(A) is controlled genetically to a major extent but some other factors like environmental and metabolic factors like diet and exercise, can modulate the Lp(A) risk factors in cardiovascular diseases. These factors can increase the prothrombotic activity of Lp(A), hence increasing the risk of cardiovascular diseases. The following image shows the relation between genetic and other metabolic factors with Lp(A) leading to alteration Lp(A) risk factor properties which causes higher CVD risks (Anuurad, Enkhmaa and Berglund, 2010).

Lipid Biomarkers (Benn, 2008)

Lipid Biomarkers (Benn, 2008)

It is also suggested that Lp(a) levels can be measured and controlled to prevent the cardiovascular diseases. Lowering the Lp (A) levels in plasma will act as therapy which will be beneficial to the patients who are at high risk of cardiovascular diseases, in order to reduce major coronary events.

There are also some apolipoproteins which function as biomarkers to improve the prediction of cardiovascular disease. Apo B, which is a primary apolipoprotein of LDL and intermediate density lipoprotein, is one of the biomarker of cardiovascular diseases (Benn, 2008). High levels of apo B are indicative of high risk and can be visualized easily in conditions where even the LDL levels remains low due to some metabolic state like type-2 diabetes (Mora, Buring and Ridker, 2014). Apo A-I is a apolipoproteins in high-density lipoprotein particles and it is a more accurate biomarker in reflecting the potential risk of Coronary Artery Disease (Walldius et al., 2001).

Lipoproteins acts as an important biomarker for the detection of cardiovascular disease. Lipoprotein (A) causes the cardiovascular diseases by the following actions mainly:

  • it inhibits the activation of plasminogen
  • it inhibits the activation of transforming growth factors
  • activates acute inflammation
  • it elevates the production of cytokines in the body.

These all factors eventually contribute to arthrosclerosis leading to cardiovascular diseases. Therefore, lowering the Lp(a) levels in the body are useful as a therapy to minimize the risk of cardiovascular diseases.

References

  • Anuurad, E., Enkhmaa, B. and Berglund, L. (2010) ‘Enigmatic Role of Lipoprotein(a) in Cardiovascular Disease’, Clinical and Translational Science, 3(6), pp. 327–332. doi: 10.1111/j.1752-8062.2010.00238.x.
  • Benn, M. (2008) ‘Common and rare alleles in apolipoprotein B contribute to plasma levels of low- density lipoprotein cholesterol in the general population’, The Journal of clinical endocrinology and metabolism Clinical, 93(3).
  • Lamon-Fava, S. et al. (2011) ‘Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study’, Journal of Lipid Research, 52(6), pp. 1181–1187. doi: 10.1194/jlr.M012526.
  • Malaguarnera, M. et al. (2013) ‘Lipoprotein(a) in cardiovascular diseases’, BioMed Research International, 2013. doi: 10.1155/2013/650989.
  • Mora, S., Buring, J. E. and Ridker, P. M. (2014) ‘Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events’, Circulation, 129(5), pp. 553–561. doi: 10.1161/CIRCULATIONAHA.113.005873.
  • Sandhu, P. K. et al. (2016) ‘Lipoprotein Biomarkers and Risk of Cardiovascular Disease: A Laboratory Medicine Best Practices (LMBP) Systematic Review’, J Appl Lab Med, 1(2), pp. 214–229. doi: 10.1373/jalm.2016.021006.
  • Walldius, G. et al. (2001) ‘High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): A prospective study’, Lancet, 358(9298), pp. 2026–2033. doi: 10.1016/S0140-6736(01)07098-2.

Diksha Tomer

Research Analyst at Project Guru
She is a bachelor in Botany honours from Miranda House (Delhi University) and is pursuing her master’s in Plant Biotechnology at TERI SAS. She is a recipient of Hemendra Kothari Scholarship and her interests lie in the field of Bioinformatics and Biotechnology.
Diksha Tomer

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