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STEM CELLS IN CARDIOVASCULAR DISEASE

Cardiovascular Disease

Cardiovascular disease has been recognised for many decades as the worldwide leading cause of death because of limited therapies available for its prevention (Huffman and Bhatnagar, 2011). The condition is characterised by narrowing of blood vessels leading to life-threatening events such as heart attack, chest pain, or stroke. With the life-threatening complications, CVD is considered the leading cause of death globally (Li et al., 2018). One of the risk factors for the disease is high blood pressure, which continues to be inadequately diagnosed and treated. However, high blood pressure control rates are low all over the world (Bâ et al., 2018). The increasing amount of exposure to risk factors is alarming, hence the necessity to promote a healthy lifestyle. Over the past two decades, numerous studies focus on the role of stem cell in the treatment of cardiac diseases. In their research, Rosen et al. (2014), focused on the use of stem cell therapies for the future treatment of cardiac diseases. In this case, regenerative medicine has been considered to be a practical approach for the replacement of dysfunctional cells including heart disease (Rosen et al., 2014). In the past two decades, various stem cells therapies have been administered in the treatment of patients with cardiac disease due to failure of conventional intervention strategies.

Smooth Muscle Cell in Cardiovascular Disease

Vascular smooth muscles play a significant in the pathogenesis of CVD (Rivard, 2000)  Blood vessels are made up of vascular smooth muscles, which play a crucial role in the development of atherosclerosis disorder present in cardiovascular disease (Li et al., 2018). They are essential components of vascular wall characterised by phenotypic plasticity in sustaining vascular homeostasis (Li et al., 2018). SMC exhibits remarkable flexibility, thus, it is essential to determine its role in CVD. Many vascular disorders resulting in CVD are caused by pathological VSMC remodelling due to injury (Martin, 2018). Despite available therapies, incidences of CVD continue, suggesting the need to identify effective therapeutic interventions.

Mesenchymal Stem Cells in Cardiovascular Disease

In recent years, substantial clinical advances in the use of mesenchymal stem cells therapies to treat CVD have emerged. According to Trivedi et al. (2010), MSC therapy represents a great opportunity in clinical management of cardiac diseases.  Among other cell types, MSCs is widely used in the regeneration and repair of cardiac muscles (Karantalis and Hare, 2015). The idea of using stem cells has emerged as an alternative approach for cellular therapies. MSCs are considered an attractive tool for cardiac remodelling and proliferation (Karantalis and Hare, 2015). They are isolated from the bone marrow and adipose tissue due to their ability to differentiating into cardiomyocytes for the induction of cardiac repair (White et al., 2016). Consequently, MSCs possesses broad differentiation potential in moderating host immune responses to promote tissue remodelling. Therefore, the use of MSCs in the treatment of CVD improves cardiac functions and reduces tissue injury.

Resident Vascular Stem Cells in Cardiovascular Disease

Vascular resident stem cells play a significant role in muscle growth and repair after vascular injury (Kovacic and Boehm, 2009). Hh pathways play a significant role in tissue morphogenesis during embryonic development and regulate renewal of adult stem cell. The discovery of resident vascular stem cells has transformed the initial understanding of the part of vascular smooth muscle cells in muscle repair and overall disease progression (Mooney et al., 2015). Hedgehog signalling pathways have become essential in cell recapitulation after vascular injury and maintenance of resident vascular stem cells (Mooney et al., 2015). As such Hh signalling contributes to investigating the predisposing factors to vascular diseases. Therefore, it is important to understand the role of vascular remodelling to develop new therapies to cure CVD.

Role of Sonic Hedgehog Protein in Cardiovascular Disease

Further, sonic hedgehog protein plays a significant role in embryonic tissue developmental patterning and regulation of morphogenesis. Sonic hedgehog (Shh) is important in the vascular system in the signalling of the endothelial cells and remodelling of blood vessels. In adult blood vessels, Shh is used in the physiological process of angiogenesis to form new blood vessels and protects the cardiac muscles against chronic ischemia (Passman et al., 2008). Moreover, Shh can stimulate angiogenic factors to facilitate cell to cell communication during vascular development and adult wound repair (Passman et al., 2008). Overall, Shh signalling in the connective tissue of an organ and the vascular cell contribute to remodelling and repair the vessel wall of the tissues.  As a result, the signalling protein pathways are often recapitulated in adults to regulate cardiac and vascular development following diseases or injury (Redmond et al., 2011). Therefore, the hedgehog protein is a fundamental signalling pathway in stem-cell maintenance and repair of cardiac ischemia. 

References

Bâ, H., Menta, I., Sangare, I., Camara, Y., Sidibe, N., Coulibaly, S., Traoré, D., Dakouo, R., Samaké, S., Traoré, A., Sidibé, S., Cissouma, M., Fofana, C., Sidibe, L. and Sanogo, K. 2018. Hypertension in Clinical Practice: Control Rate in Short Term and Associated Factors in the Cardiology Department of the University Hospital Gabriel Touré (UH-GT) in Bamako (Mali). World Journal of Cardiovascular Diseases, 08(06), pp.288-297.

Huffman, M. and Bhatnagar, D. (2011). Novel Treatments for Cardiovascular Disease Prevention. Cardiovascular Therapeutics, 30(5), pp.257-263.

Karantalis, V. and Hare, J. 2015. Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease. Circulation Research, 116(8), pp.1413-1430.

Kovacic, J. and Boehm, M. (2009). Resident vascular progenitor cells: An emerging role for non-terminally differentiated vessel-resident cells in vascular biology. Stem Cell Research, 2(1), pp.2-15.

Li, M., Qian, M., Kyler, K. and Xu, J. 2018. Endothelial–Vascular Smooth Muscle Cells Interactions in Atherosclerosis. Frontiers in Cardiovascular Medicine, 5.

Martin, K., 2018. Epigenetic control of vascular smooth muscle in cardiovascular disease. [online] Grantome. Available at: <http://grantome.com/grant/NIH/R01-HL119529-01A1> [Accessed 26 Oct. 2018].

Mooney, C., Hakimjavadi, R., Fitzpatrick, E., Kennedy, E., Walls, D., Morrow, D., Redmond, E. and Cahill, P. (2015). Hedgehog and Resident Vascular Stem Cell Fate. Stem Cells International, 2015, pp.1-16.

Passman, J., Dong, X., Wu, S., Maguire, C., Hogan, K., Bautch, V. and Majesky, M. (2008). A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells. Proceedings of the National Academy of Sciences, 105(27), pp.9349-9354.

Rivard A, R. (2000). Vascular smooth muscle cell proliferation in the pathogenesis of atherosclerotic cardiovascular diseases. Histol Histopathol 15(2), pp. 557-71.

Redmond, E., Guha, S., Walls, D. and Cahill, P. 2011. Investigational Notch and Hedgehog inhibitors – therapies for cardiovascular disease. Expert Opinion on Investigational Drugs, 20(12), pp.1649-1664.

Rosen, M., Myerburg, R., Francis, D., Cole, G. and Marbán, E. (2014). Translating Stem Cell Research to Cardiac Disease Therapies. Journal of the American College of Cardiology, 64(9), pp.922-937.

Trivedi, P., Tray, N., Nguyen, T., Nigam, N. and Gallicano, G. (2010). Mesenchymal Stem Cell Therapy for Treatment of Cardiovascular Disease: Helping People Sooner or Later. Stem Cells and Development, 19(7), pp.1109-1120.

Wang, D., Li, L., Dai, T., Wang, A. and Li, S. (2018). Adult Stem Cells in Vascular Remodeling. Theranostics, 8(3), pp.815-829.

White, I., Sanina, C., Balkan, W. and Hare, J. 2016. Mesenchymal Stem Cells in Cardiology. Mesenchymal Stem Cells, pp.55-87.

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