From the Laboratory to the Clinic: Molecular Treatment of Heart Failure

Yıl 2024, Cilt: 26 Sayı: 1, 3 - 8, 30.04.2024

Mehmet Alagoz , Merve Alpay

https://doi.org/10.18678/dtfd.1435020

Öz

Coronary and cardiovascular diseases are the leading cause of death today, with heart failure being among the primary culprits. Heart failure can occur as a result of many diseases, so research in this area is important in terms of clinical outcomes and treatment. Histopathology of heart failure includes cardiac hypertrophy, inflammation, angiogenesis, and apoptosis pathways. The issue of elucidating the pathology of heart failure is still an area of active research. In advanced heart failure, the typical management strategy is medical treatment, mechanical ventricular support devices, and heart transplantation. Heart failure, which occurs with modifiable and non-modifiable risk factors, can be controlled with both non-pharmacological and pharmacological treatment applications. It is especially important to focus on new treatment methods and introduce them to the clinic. Although they are all not yet used in clinics, many studies have yielded promising results with molecular treatment options for heart failure prevention. Studies in animals have shown that heart failure stops proceeding when angiogenesis is induced. Promising results have also been achieved with stem cell therapy, but these may not be implementable for years. It is expected that studies following phases 1 and 2, of the studies which had positive results in the treatment of heart failure, will be conducted and applied in the daily treatment practice.

Anahtar Kelimeler

Heart failure, molecular treatment, stem cell therapy

Laboratuvardan Kliniğe: Kalp Yetmezliğinin Moleküler Tedavisi

Öz

Koroner ve kalp-damar hastalıkları günümüzün önde gelen ölüm nedenidir; kalp yetmezliği ise primer etiyoloji arasında yer almaktadır. Kalp yetmezliği birçok hastalığın getirisi olarak ortaya çıkabildiğinden bu alanda yapılacak araştırmalar klinik sonuçlar ve tedavi açısından önemlidir. Kalp yetmezliğinin histopatolojisi, kalp hipertrofisi, inflamasyon, anjiyogenez ve apoptoz yolaklarını içerir. Kalp yetmezliği patolojisinin aydınlatılması konusu halen aktif bir araştırma alanıdır. İlerlemiş kalp yetmezliğinde tipik tedavi stratejisi tıbbi tedavi, mekanik ventriküler destek cihazları ve kalp naklidir. Değiştirilebilen ve değiştirilemeyen risk faktörleriyle ortaya çıkan kalp yetmezliği hem farmakolojik hem de non-farmakolojik tedavi uygulamalarıyla kontrol altına alınabilmektedir. Özellikle yeni tedavi yöntemlerine odaklanılması ve bunların kliniğe tanıtılması önemlidir. Henüz klinikte kullanılmamasına rağmen, birçok çalışma kalp yetmezliğinin önlenmesine yönelik moleküler tedavi seçenekleriyle umut verici sonuçlar vermiştir. In vivo yapılan çalışmalar, anjiyogenez uyarıldığında kalp yetmezliğinin ilerlemesinin durduğunu göstermiştir. Kök hücre tedavisinde de umut verici sonuçlar alınmakta iken aktif uygulama yapılamamaktadır. Kalp yetmezliği tedavisinde olumlu sonuç alınan çalışmalardan faz 1 ve 2. aşamayı takip eden çalışmaların yapılması ve günlük tedavi pratiğinde uygulanması beklenmektedir.

Anahtar Kelimeler

Kalp yetmezliği, moleküler tedavi, kök hücre terapi

Kaynakça

• Xu J, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final data for 2016. Natl Vital Stat Rep. 2018;67(5):1-76.
• Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56-e528.
• Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al.; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891-975.
• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al.; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-327.
• van Riet EE, Hoes AW, Limburg A, Landman MA, van der Hoeven H, Rutten FH. Prevalence of unrecognized heart failure in older persons with shortness of breath on exertion. Eur J Heart Fail. 2014;16(7):772-7.
• Thibodeau JT, Drazner MH. The Role of the clinical examination in patients with heart failure. JACC Heart Fail. 2018;6(7):543-51.
• Khalid K, Padda J, Komissarov A, Colaco LB, Padda S, Khan AS, et al. The coexistence of chronic obstructive pulmonary disease and heart failure. Cureus. 2021;13(8):e17387.
• Hamzeh N, Ghadimi F, Farzaneh R, Hosseini SK. Obesity, heart failure, and obesity paradox. J Tehran Heart Cent. 2017;12(1):1-5.
• Del Gobbo LC, Kalantarian S, Imamura F, Lemaitre R, Siscovick DS, Psaty BM, et al. Contribution of major lifestyle risk factors for incident heart failure in older adults: the cardiovascular health study. JACC Heart Fail. 2015;3(7):520-8.
• Honeyman E, Ding H, Varnfield M, Karunanithi M. Mobile health applications in cardiac care. Interv Cardiol. 2014;6(2):227-40.
• Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2018 Update: a report from the American Heart Association. Circulation. 2018;137(12):e67-e492.
• Senecal C, Widmer RJ, Johnson MP, Lerman LO, Lerman A. Digital health intervention as an adjunct to a workplace health program in hypertension. J Am Soc Hypertens. 2018;12(10):695-702.
• Miao H, Zou C, Yang S, Chia YC, Van Huynh M, Sogunuru GP, et al. Targets and management of hypertension in heart failure: focusing on the stages of heart failure. J Clin Hypertens (Greenwich). 2022;24(9):1218-25.
• Bosworth HB, Powers BJ, Olsen MK, McCant F, Grubber J, Smith V, et al. Home blood pressure management and improved blood pressure control. Arch Intern Med. 2011;171(13):1173-80.
• Chatterjee NA, Chae CU, Kim E, Moorthy MV, Conen D, Sandhu RK, et al. Modifiable risk factors for incident heart failure in atrial fibrillation. JACC Heart Fail. 2017;5(8):552-60.
• Muse ED, Torkamani A, Topol EJ. When genomics goes digital. Lancet. 2018;391(10138):2405.
• Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219-24.
• Li C, Pan Y, Zhang R, Huang Z, Li D, Han Y, et al. Genomic innovation in early life cardiovascular disease prevention and treatment. Circ Res. 2023;132(12):1628-47.
• Wongvibulsin S, Martin SS, Steinhubl SR, Muse ED. Connected health technology for cardiovascular disease prevention and management. Curr Treat Options Cardiovasc Med. 2019;21(6):29.
• Dhruva SS, Ross JS, Mortazavi BJ, Hurley NC, Krumholz HM, Curtis JP, et al. Use of mechanical circulatory support devices among patients with acute myocardial infarction complicated by cardiogenic shock. JAMA Netw Open 2021;4(2):e2037748.
• Severino P, D'Amato A, Prosperi S, Myftari V, Canuti ES, Labbro Francia A, et al. Heart failure pharmacological management: gaps and current perspectives. J Clin Med. 2023;12(3):1020.
• Jerez Castro AM. Non-pharmacological approaches in heart failure. CorSalud. 2020;12(2):198-208.
• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):1810-52.
• Westerdahl DE, Kobashigawa JA. Heart transplantation for advanced heart failure. Cardiac Intensive Care 2019:504-24.e2.
• Kara M, Özçağlı E, Tarbın Jannuzzi A, Alpertunga B. Oxidative stress mediated cardiac apoptosis. Istanbul J Pharm. 2015;45(2):217-32.
• Hong JH, Zhang HG. Transcription factors involved in the development and prognosis of cardiac remodeling. Front Pharmacol. 2022;13:828549.
• Hsu A, Duan Q, Day DS, Luo X, McMahon S, Huang Y, et al. Targeting transcription in heart failure via CDK7/12/13 inhibition. Nat Commun. 2022;13(1):4345.
• Heger J, Schulz R, Euler G. Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure. Br J Pharmacol. 2016;173(1):3-14.
• Marian AJ. Molecular genetic basis of hypertrophic cardiomyopathy. Circ Res. 2021;128(10):1533-53.
• Hartupee J, Mann DL. Neurohormonal activation in heart failure with reduced ejection fraction. Nat Rev Cardiol. 2017;14(1):30-8.
• Saraf A, Rampoldi A, Chao M, Li D, Armand L, Hwang H, et al. Functional and molecular effects of TNF-α on human iPSC-derived cardiomyocytes. Stem Cell Res. 2021;52:102218.
• Hilfiker-Kleiner D, Hilfiker A, Drexler H. Many good reasons to have STAT3 in the heart. Pharmacol Ther. 2005;107(1):131-7.
• Anversa P, Kajstura J, Leri A, Bolli R. Life and death of cardiac stem cells: a paradigm shift in cardiac biology. Circulation. 2006;113(11):1451-63.
• Hilfiker-Kleiner D, Landmesser U, Drexler H. Molecular mechanisms in heart failure: focus on cardiac hypertrophy, inflammation, angiogenesis, and apoptosis. J Am Coll Cardiol. 2006;48(9):A56-66.
• Podewski EK, Hilfiker-Kleiner D, Hilfiker A, Morawietz H, Lichtenberg A, Wollert KC, et al. Alterations in Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in patients with end-stage dilated cardiomyopathy. Circulation. 2003;107(6):798-802.
• Hayakawa Y, Chandra M, Miao W, Shirani J, Brown JH, Dorn GW 2nd, et al. Inhibition of cardiac myocyte apoptosis improves cardiac function and abolishes mortality in the peripartum cardiomyopathy of Galpha(q) transgenic mice. Circulation. 2003;108(24):3036-41.
• Banquet S, Gomez E, Nicol L, Edwards-Lévy F, Henry JP, Cao R, et al. Arteriogenic therapy by intramyocardial sustained delivery of a novel growth factor combination prevents chronic heart failure. Circulation. 2011;124(9):1059-69.
• Deveza L, Choi J, Yang F. Therapeutic angiogenesis for treating cardiovascular diseases. Theranostics. 2012;2(8):801-14.
• Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, et al. A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest. 2003;111(10):1497-504.
• Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, et al. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res. 2004;94(4):514-24.
• Young PP, Vaughan DE, Hatzopoulos AK. Biologic properties of endothelial progenitor cells and their potential for cell therapy. Prog Cardiovasc Dis. 2007;49(6):421-9.
• Lipsett DB, Frisk M, Aronsen JM, Nordén ES, Buonarati OR, Cataliotti A, et al. Cardiomyocyte substructure reverts to an immature phenotype during heart failure. J Physiol. 2019;597(7):1833-53.
• Feng W, Ye F, Xue W, Zhou Z, Kang YJ. Copper regulation of hypoxia-inducible factor-1 activity. Mol Pharmacol. 2009;75(1):174-82.
• Kameda Y, Hasegawa H, Kubota A, Tadokoro H, Kobayashi Y, Komuro I, et al. Effects of pitavastatin on pressure overload-induced heart failure in mice. Circ J. 2012;76(5):1159-68.
• Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 2005;433(7026):647-53.
• Carr AM. Cell cycle. Piecing together the p53 puzzle. Science. 2000;287(5459):1765-6.
• Mongirdienė A, Skrodenis L, Varoneckaitė L, Mierkytė G, Gerulis J. Reactive oxygen species induced pathways in heart failure pathogenesis and potential therapeutic strategies. Biomedicines. 2022;10(3):602.
• Kühn B, del Monte F, Hajjar RJ, Chang YS, Lebeche D, Arab S, et al. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nature Med. 2007;13(8):962-9.
• Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763-76.
• Rubart M, Field LJ. Cardiac regeneration: repopulating the heart. Annu Rev Physiol. 2006;68:29-49.
• Bolli R, Tang XL. The sad plight of cell therapy for heart failure: causes and consequences. J Cardiovasc Aging. 2022;2:16.
• Zhang H, Zhan Q, Huang B, Wang Y, Wang X. AAV-mediated gene therapy: Advancing cardiovascular disease treatment. Front Cardiovasc Med. 2022;9:952755.
• Chachques JC. Cardiomyoplasty: is it still a viable option in patients with end-stage heart failure?. Eur J Cardiothorac Surg. 2009;35(2):201-3.