Despite the modern therapeutic approaches, the prognosis and outcome of myocardial infarction and subsequent chronic heart failure is still very poor: more than 50% of affected patients die within 5 years. Thus, the condition represents a huge burden on the society and on the healthcare system.
Although, there are many causes of heart failure, eventually the structure and the function of the myocardium will deteriorate, leading to the severe symptoms of heart failure. Despite the varying etiology, it seems, that both cellular (neutrophil granulocytes, monocytes and macrophages, B and T lymphocytes) and humoral (cytokines and chemokines, neuropeptides, autoantibodies) pro-inflammatory mediators play a significant role in the progression of the disease by triggering myocardial damage. We aim to study both these various cell types and different humoral factors, aiming to modulate the healing and remodeling processes during the development of chronic heart failure.
Figure 1. Stages of inflammatory cell invasion of the heart after myocardial infarction.
Varga ZV, Pipicz M, Baán JA, Baranyai T, Koncsos G, Leszek P, Kuśmierczyk M, Sánchez-Cabo F, García-Pavía P, Brenner GJ, Giricz Z, Csont T, Mendler L, Lara-Pezzi E, Pacher P, Ferdinandy P. Alternative Splicing of NOX4 in the Failing Human Heart. Front Physiol. 2017 8:935. [IF: 3.394]
Rajtik T, Goncalvesova E, Varga ZV, Leszek P, Kusmierczyk M, Hulman M, Kyselovic J, Ferdinandy P, Adameova A. Posttranslational modifications of calcium/calmodulin-dependent protein kinase IIδ and its downstream signaling in human failing hearts. Am J Transl Res. 20179:3573-3585. [IF: 3.061]
Szobi A, Gonçalvesová E, Varga ZV, Leszek P, Kuśmierczyk M, Hulman M, Kyselovič J, Ferdinandy P, Adameová A. Analysis of necroptotic proteins in failing human hearts. J Transl Med. 2017 15:86. [IF: 4.197]
Baán JA, Varga ZV, Leszek P, Kuśmierczyk M, Baranyai T, Dux L, Ferdinandy P, Braun T, Mendler L. Myostatin and IGF-I signaling in end-stage human heart failure: a qRT-PCR study. J Transl Med. 2015 16;13:1. [IF: 4.197]
Heart failure often develops in patients with metabolic syndrome. This form of the disease is called heart failure with preserved ejection fraction, and the patients suffering from HFpEF are typically elderly and have multiple co-morbidities (diabetes, obesity, hypertension), and the 5-year mortality of the disease is really high (65%). Therefore, there is an unmet need to better understand the pathomechanism of HFpEF, and to develop new therapies for these patients, since the classic drugs (ACE inhibitors, Beta adrenoreceptor antagonists, etc.) used in the treatment of congestive heart failure are not effective in this patient population.
We hypothesize that cardiac dysfunction is triggered in HFpEF by a systemic inflammatory state, however, to dissect the pathogenic components of inflammation, there is further extensive research needed. We are further limited in understanding HFpEF by the currently available animal models, that are restricted to study only specific aspect of the complex disease. Therefore, we aim to develop new animal models that reflect several aspect of the human condition, and we will test new therapies to this important condition.
Fig. 3. Clinical characteristics of HFpEF
Valenta I*, Varga ZV*, Valentine H, Cinar R, Horti A, Mathews WB, Dannals RF, Steele K, Kunos G, Wahl RL, Pomper MG, Wong DF, Pacher P, Schindler TH. Feasibility Evaluation of Myocardial Cannabinoid Type 1 Receptor Imaging in Obesity: A Translational Approach. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 2):320-332. [IF: 10.189] *-shared first authorship
Varga ZV, Kupai K, Szűcs G, Gáspár R, Pálóczi J, Faragó N, Zvara A, Puskás LG, Rázga Z, Tiszlavicz L, Bencsik P, Görbe A, Csonka C, Ferdinandy P, Csont T.: MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart. J Mol Cell Cardiol. 2013. 62:111-21. [IF: 5.218]