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Differences Between the Pathophysiology of Myocardial Infarction Related Cardiomyopathy and Anthracycline Related Cardiomyopathy

Tjerk Scheepstra, Tjerk (2019) Differences Between the Pathophysiology of Myocardial Infarction Related Cardiomyopathy and Anthracycline Related Cardiomyopathy. Bachelor's Thesis, Biology.

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Abstract

Anthracyclines have shown to be very useful in treating cancers, but have received a lot of attention lately due to their cardiotoxic side effects causing cardiomyopathy (CM). Sufficient therapy has not yet been developed due to differences in injury pathways and mechanisms compared to other CM’s. Moreover, the pathophysiology of anthracycline caused CM is not fully understood. Therefore, the aim of this review is to inform the reader about specialities of this type of cardiomyopathy, along with the latest therapeutic insights. This is done by comparing differences and similarities with a more known type of CM, namely myocardial infarction caused CM. Differences and similarities in the pathophysiology between the two CM’s originate from typical molecular mechanisms causing cardiac injury. They share ROS generation as a big injury mediator, but also have its own unique pathways of causing cardiac injury like Ca2+ overload and Topoisomerase IIB binding. Cellular apoptosis and necrosis is witnessed in both cases, but cardiomyocytes differ in their reaction to the disease when looked at size adaptation. Cardiomyocytes after MI undergo eccentric hypertrophy while they undergo atrophy after anthracycline treatment. More differences are seen in autophagy regulation and the way of collagen deposition. Cellular changes eventually lead to physiological changes characterised by LV wall thinning, unevenly divided wall tension, scar formation, left ventricle (LV) dilation and LV dysfunction. Only the last two characteristics are shared by anthracycline mediated CM, which is further distinguished by its loss in LV wall mass. Both forms of CM have shown to respond positively to ACE inhibitors. Further current therapies, though not sufficient enough, are already present for MI related CM, but not for anthracyclines. Promising new therapies for Anthracycline treatment are mostly aimed at preventing oxidative damage. Targeting Nrf2, NF-kB and autophagy/mitophagy pathways have all shown very promising results in animal studies. However, clinical studies remain to be executed.

Item Type: Thesis (Bachelor's Thesis)
Supervisor:
Supervisor nameSupervisor E mail
Harmsen, M.C.m.c.harmsen@umcg.nl
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 16 Jul 2019
Last Modified: 16 Jul 2019 13:47
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/20246

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