ALTERATIONS IN THE PERIPHERAL CIRCULATION IN HEART FAILURE: CURRENT VIEW ON ENDOTHELIAL DYSFUNCTION AND PHARMACOLOGICAL IMPLICATIONS INVOLVING ITS PATHOPHYSIOLOGICAL ASPECTS
ARTICLE PDF

Keywords

peripheral circulation
heart failure
endothelial dysfunction
pathophysiology
pharmacological implication

How to Cite

Chursina, T., Kravchenko, A., & Mikhaliev, K. (2022). ALTERATIONS IN THE PERIPHERAL CIRCULATION IN HEART FAILURE: CURRENT VIEW ON ENDOTHELIAL DYSFUNCTION AND PHARMACOLOGICAL IMPLICATIONS INVOLVING ITS PATHOPHYSIOLOGICAL ASPECTS. Clinical and Preventive Medicine, (2), 42-51. https://doi.org/10.31612/2616-4868.2(20).2022.05

Abstract

Introduction. Despite the significant advances in the pharmacotherapy of cardiovascular diseases, the increasing prevalence of heart failure (HF) and its poor prognosis constitute one of the leading medical problems worldwide. The complex pathophysiology of HF involves the alterations in the peripheral circulation, particularly the development of endothelial dysfunction (ED). The deepening of understanding the pathology of ED and the spectrum of pharmacological implications, involving its certain pathophysiological aspects, could favor the optimization of the personalized approach to the management of such challenging HF patients.

Aim: to provide a literature review of the current data on the alterations in peripheral circulation in HF with the focus on ED, and to outline possible pharmacological implications involving certain pathophysiological aspects of ED in HF patients.

Material and methods. The thematic scientific papers, published predominantly during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis.

Results and discussion. Currently, the ED considered as a stage of a specific continuum, which is initiated in the form of «activation» of the endothelium, and moves through the stage of its actual «dysfunction» to the stage of endothelial «damage». Taking into account the important pathogenetic and prognostic significance of ED in HF, the endothelium is considered as a target of various pharmacological influences, including renin-angiotensin-aldosterone inhibitors and statins. Among the modern approaches to pharmacological treatment of HF, the correction of reduced nitric oxide (NO) bioavailability by modulating the «NO-soluble guanylate cyclase-cyclic guanosine monophosphate» signaling pathway is a perspective option in terms of preventing the occurrence and progression of ED.

Conclusion. The deepening of knowledge about the pathophysiological features of ED in HF allows both to improve the understanding of the pharmacodynamic effects of already approved cardiovascular drugs, and to outline the perspectives for pharmacological direct or indirect impact on endothelium.

https://doi.org/10.31612/2616-4868.2(20).2022.05
ARTICLE PDF

References

Libby, P., Bonow, R. O., Mann, D. L., Tomaselli, G. F., Bhatt, D., & Solomon, S. D. (2022). Braunwald's heart disease, single volume: A textbook of cardiovascular medicine (12th ed.). Elsevier.

Felker, G. M., & Mann, D. L. (2020). Heart failure: A companion to Braunwald's heart disease. Elsevier.

Fuster, V., & Narula, J. (2022). Fuster and Hurst's the heart (15th ed.). McGraw-Hill Education / Medical.

McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., Cleland, J., Coats, A., Crespo-Leiro, M. G., Farmakis, D., Gilard, M., Heymans, S., Hoes, A. W., Jaarsma, T., Jankowska, E. A., Lainscak, M., … ESC Scientific Document Group (2021). 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European heart journal, 42(36), 3599–3726. https://doi.org/10.1093/eurheartj/ehab368

Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., Fang, J. C., Fedson, S. E., Fonarow, G. C., Hayek, S. S., Hernandez, A. F., Khazanie, P., Kittleson, M. M., Lee, C. S., Link, M. S., Milano, C. A., … Yancy, C. W. (2022). 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 101161CIR0000000000001063. Advance online publication. https://doi.org/10.1161/CIR.0000000000001063

Xia, J., Hui, N., Tian, L., Liang, C., Zhang, J., Liu, J., Wang, J., Ren, X., Xie, X., & Wang, K. (2022). Development of vericiguat: The first soluble guanylate cyclase (sGC) stimulator launched for heart failure with reduced ejection fraction (HFrEF). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 149, 112894. Advance online publication. https://doi.org/10.1016/j.biopha.2022.112894

Abdin, A., Bauersachs, J., Frey, N., Kindermann, I., Link, A., Marx, N., Lainscak, M., Slawik, J., Werner, C., Wintrich, J., & Böhm, M. (2021). Timely and individualized heart failure management: need for implementation into the new guidelines. Clinical research in cardiology : official journal of the German Cardiac Society, 110(8), 1150–1158. https://doi.org/10.1007/s00392-021-01867-2

Mann, D. L., & Felker, G. M. (2021). Mechanisms and Models in Heart Failure: A Translational Approach. Circulation research, 128(10), 1435–1450. https://doi.org/10.1161/CIRCRESAHA.121.318158

Luz, P. L., Libby, P., Laurindo, F. R., & Chagas, A. C. (2018). Endothelium and cardiovascular diseases: Vascular biology and clinical syndromes. Elsevier.

Shepro, D., & D'Amore, P. (2006). Microvascular research: Biology and pathology. Elsevier.

Moncada, S., & Higgs, A. (2006). The vascular endothelium I. Springer Science & Business Media.

Moncada, S., & Higgs, A. (2006). The vascular endothelium II. Springer Science & Business Media.

Krüger-Genge, A., Blocki, A., Franke, R. P., & Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. International journal of molecular sciences, 20(18), 4411. https://doi.org/10.3390/ijms20184411

Botts, S. R., Fish, J. E., & Howe, K. L. (2021). Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment. Frontiers in pharmacology, 12, 787541. https://doi.org/10.3389/fphar.2021.787541

Sabe, S. A., Feng, J., Sellke, F. W., & Abid, M. R. (2022). Mechanisms and clinical implications of endothelium-dependent vasomotor dysfunction in coronary microvasculature. American journal of physiology. Heart and circulatory physiology, 322(5), H819–H841. https://doi.org/10.1152/ajpheart.00603.2021

Gallo, G., Volpe, M., & Savoia, C. (2022). Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Frontiers in medicine, 8, 798958. https://doi.org/10.3389/fmed.2021.798958

Segers, V., Brutsaert, D. L., & De Keulenaer, G. W. (2018). Cardiac Remodeling: Endothelial Cells Have More to Say Than Just NO. Frontiers in physiology, 9, 382. https://doi.org/10.3389/fphys.2018.00382

Zuchi, C., Tritto, I., Carluccio, E., Mattei, C., Cattadori, G., & Ambrosio, G. (2020). Role of endothelial dysfunction in heart failure. Heart failure reviews, 25(1), 21–30. https://doi.org/10.1007/s10741-019-09881-3

Lam, C. S., & Lund, L. H. (2016). Microvascular endothelial dysfunction in heart failure with preserved ejection fraction. Heart (British Cardiac Society), 102(4), 257–259. https://doi.org/10.1136/heartjnl-2015-308852

Gladwin M. T. (2021). Endothelium Seeing Red: Should We Redefine eNOS as the Endothelial and Erythrocytic NOS?. Circulation, 144(11), 890–892. https://doi.org/10.1161/CIRCULATIONAHA.121.055679

Kassis-George, H., Verlinden, N. J., Fu, S., & Kanwar, M. (2022). Vericiguat in Heart Failure with a Reduced Ejection Fraction: Patient Selection and Special Considerations. Therapeutics and clinical risk management, 18, 315–322. https://doi.org/10.2147/TCRM.S357422

Sandner, P., Follmann, M., Becker-Pelster, E., Hahn, M. G., Meier, C., Freitas, C., Roessig, L., & Stasch, J. P. (2021). Soluble GC stimulators and activators: Past, present and future. British journal of pharmacology, 10.1111/bph.15698. Advance online publication. https://doi.org/10.1111/bph.15698

Tran, B. A., Serag-Bolos, E. S., Fernandez, J., & Miranda, A. C. (2022). Vericiguat: The First Soluble Guanylate Cyclase Stimulator for Reduction of Cardiovascular Death and Heart Failure Hospitalization in Patients With Heart Failure Reduced Ejection Fraction. Journal of pharmacy practice, 8971900221087096. Advance online publication. https://doi.org/10.1177/08971900221087096

Lang, N. N., Dobbin, S., & Petrie, M. C. (2020). Vericiguat in worsening heart failure: agonising over, or celebrating, agonism in the VICTORIA trial. Cardiovascular research, 116(12), e152–e155. https://doi.org/10.1093/cvr/cvaa247

Helms, C. C., Gladwin, M. T., & Kim-Shapiro, D. B. (2018). Erythrocytes and Vascular Function: Oxygen and Nitric Oxide. Frontiers in physiology, 9, 125. https://doi.org/10.3389/fphys.2018.00125

Asaro, R. J., & Cabrales, P. (2021). Red Blood Cells: Tethering, Vesiculation, and Disease in Micro-Vascular Flow. Diagnostics (Basel, Switzerland), 11(6), 971. https://doi.org/10.3390/diagnostics11060971

Weisel, J. W., & Litvinov, R. I. (2019). Red blood cells: the forgotten player in hemostasis and thrombosis. Journal of thrombosis and haemostasis : JTH, 17(2), 271–282. https://doi.org/10.1111/jth.14360

Leo, F., Suvorava, T., Heuser, S. K., Li, J., LoBue, A., Barbarino, F., Piragine, E., Schneckmann, R., Hutzler, B., Good, M. E., Fernandez, B. O., Vornholz, L., Rogers, S., Doctor, A., Grandoch, M., Stegbauer, J., Weitzberg, E., Feelisch, M., Lundberg, J. O., Isakson, B. E., … Cortese-Krott, M. M. (2021). Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure. Circulation, 144(11), 870–889. https://doi.org/10.1161/CIRCULATIONAHA.120.049606

Lugo-Gavidia, L. M., Burger, D., Matthews, V. B., Nolde, J. M., Galindo Kiuchi, M., Carnagarin, R., Kannenkeril, D., Chan, J., Joyson, A., Herat, L. Y., Azzam, O., & Schlaich, M. P. (2021). Role of Microparticles in Cardiovascular Disease: Implications for Endothelial Dysfunction, Thrombosis, and Inflammation. Hypertension (Dallas, Tex. : 1979), 77(6), 1825–1844. https://doi.org/10.1161/HYPERTENSIONAHA.121.16975

Thangaraju, K., Neerukonda, S. N., Katneni, U., & Buehler, P. W. (2020). Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy. International journal of molecular sciences, 22(1), 153. https://doi.org/10.3390/ijms22010153

Misiti, F., Carelli-Alinovi, C., & Rodio, A. (2022). ATP release from erythrocytes: A role of adenosine. Clinical hemorheology and microcirculation, 80(2), 61–71. https://doi.org/10.3233/CH-221379

Chiangjong, W., Netsirisawan, P., Hongeng, S., & Chutipongtanate, S. (2021). Red Blood Cell Extracellular Vesicle-Based Drug Delivery: Challenges and Opportunities. Frontiers in medicine, 8, 761362. https://doi.org/10.3389/fmed.2021.761362

Buttari, B., Profumo, E., & Riganò, R. (2015). Crosstalk between red blood cells and the immune system and its impact on atherosclerosis. BioMed research international, 2015, 616834. https://doi.org/10.1155/2015/616834

Jeney, V., Balla, G., & Balla, J. (2014). Red blood cell, hemoglobin and heme in the progression of atherosclerosis. Frontiers in physiology, 5, 379. https://doi.org/10.3389/fphys.2014.00379

Tziakas, D. N., Chalikias, G. K., Stakos, D., & Boudoulas, H. (2010). The role of red blood cells in the progression and instability of atherosclerotic plaque. International journal of cardiology, 142(1), 2–7. https://doi.org/10.1016/j.ijcard.2009.10.031

Tziakas, D., Chalikias, G., Kapelouzou, A., Tentes, I., Schäfer, K., Karayannakos, P., Kostakis, A., Boudoulas, H., & Konstantinides, S. (2013). Erythrocyte membrane cholesterol and lipid core growth in a rabbit model of atherosclerosis: modulatory effects of rosuvastatin. International journal of cardiology, 170(2), 173–181. https://doi.org/10.1016/j.ijcard.2013.10.070

Loyer, X., Vion, A. C., Tedgui, A., & Boulanger, C. M. (2014). Microvesicles as cell-cell messengers in cardiovascular diseases. Circulation research, 114(2), 345–353. https://doi.org/10.1161/CIRCRESAHA.113.300858

Papadopoulos, C., Tentes, I., & Anagnostopoulos, K. (2021). Lipotoxicity Disrupts Erythrocyte Function: A Perspective. Cardiovascular & hematological disorders drug targets, 21(2), 91–94. https://doi.org/10.2174/1871529X21666210719125728

Tziakas, D. N., Chalikias, G., Pavlaki, M., Kareli, D., Gogiraju, R., Hubert, A., Böhm, E., Stamoulis, P., Drosos, I., Kikas, P., Mikroulis, D., Giatromanolaki, A., Georgiadis, G. S., Konstantinou, F., Argyriou, C., Münzel, T., Konstantinides, S. V., & Schäfer, K. (2019). Lysed Erythrocyte Membranes Promote Vascular Calcification. Circulation, 139(17), 2032–2048. https://doi.org/10.1161/CIRCULATIONAHA.118.037166

Dreischer, P., Duszenko, M., Stein, J., & Wieder, T. (2022). Eryptosis: Programmed Death of Nucleus-Free, Iron-Filled Blood Cells. Cells, 11(3), 503. https://doi.org/10.3390/cells11030503

Byrnes, J. R., & Wolberg, A. S. (2017). Red blood cells in thrombosis. Blood, 130(16), 1795–1799. https://doi.org/10.1182/blood-2017-03-745349

Münzel, T., Gori, T., Keaney, J. F., Jr, Maack, C., & Daiber, A. (2015). Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. European heart journal, 36(38), 2555–2564. https://doi.org/10.1093/eurheartj/ehv305

Campbell, N., Kalabalik-Hoganson, J., & Frey, K. (2022). Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure. The Annals of pharmacotherapy, 56(5), 600–608. https://doi.org/10.1177/10600280211041384

Park, M., Sandner, P., & Krieg, T. (2018). cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway. Basic research in cardiology, 113(4), 24. https://doi.org/10.1007/s00395-018-0679-9

Yu, J. D., & Miyamoto, S. (2021). Molecular Signaling to Preserve Mitochondrial Integrity against Ischemic Stress in the Heart: Rescue or Remove Mitochondria in Danger. Cells, 10(12), 3330. https://doi.org/10.3390/cells10123330

Erdmann, E., Semigran, M. J., Nieminen, M. S., Gheorghiade, M., Agrawal, R., Mitrovic, V., & Mebazaa, A. (2013). Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. European heart journal, 34(1), 57–67. https://doi.org/10.1093/eurheartj/ehs196

Armstrong, P. W., Pieske, B., Anstrom, K. J., Ezekowitz, J., Hernandez, A. F., Butler, J., Lam, C., Ponikowski, P., Voors, A. A., Jia, G., McNulty, S. E., Patel, M. J., Roessig, L., Koglin, J., O'Connor, C. M., & VICTORIA Study Group (2020). Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. The New England journal of medicine, 382(20), 1883–1893. https://doi.org/10.1056/NEJMoa1915928

Schirone, L., Forte, M., D'Ambrosio, L., Valenti, V., Vecchio, D., Schiavon, S., Spinosa, G., Sarto, G., Petrozza, V., Frati, G., & Sciarretta, S. (2022). An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives. Cells, 11(7), 1165. https://doi.org/10.3390/cells11071165

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.