Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren-2 transgenic (TGR) rats and a volume-overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41-8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague-Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP-2, TGF-β, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR-ACF rats receiving sGC stimulators. Notably, all untreated TGR-ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.

• Klíčová slova
• heart failure with reduced ejection fraction, reactive oxygen/nitrogen species, renin‐angiotensin system, soluble guanylate cyclase stimulator,
• MeSH
• agonisté guanylátcyklasy * farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• morfoliny MeSH
• oxidační stres účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• pyrazoly * farmakologie   terapeutické užití   MeSH
• pyrimidiny * farmakologie   terapeutické užití   MeSH
• remodelace komor účinky léků   MeSH
• rozpustná guanylátcyklasa * metabolismus   MeSH
• srdeční selhání * farmakoterapie   etiologie   patofyziologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté guanylátcyklasy * MeSH
• BAY 41-8543 MeSH Prohlížeč
• morfoliny MeSH
• pyrazoly * MeSH
• pyrimidiny * MeSH
• rozpustná guanylátcyklasa * MeSH

Cardiovascular diseases (CVDs) are a group of disorders affecting the heart and blood vessels and a leading cause of death worldwide. Thus, there is a need to identify new cardiokines that may protect the heart from damage as reported in GBD 2017 Causes of Death Collaborators (2018) (The Lancet 392:1736-1788). Follistatin-like 1 (FSTL1) is a cardiokine that is highly expressed in the heart and released to the serum after cardiac injury where it is associated with CVD and predicts poor outcome. The action of FSTL1 likely depends not only on the tissue source but also post-translation modifications that are target tissue- and cell-specific. Animal studies examining the effect of FSTL1 in various models of heart disease have exploded over the past 15 years and primarily report a protective effect spanning from inhibiting inflammation via transforming growth factor, preventing remodeling and fibrosis to promoting angiogenesis and hypertrophy. A better understanding of FSTL1 and its homologs is needed to determine whether this protein could be a useful novel biomarker to predict poor outcome and death and whether it has therapeutic potential. The aim of this review is to provide a comprehensive description of the literature for this family of proteins in order to better understand their role in normal physiology and CVD.

• Klíčová slova
• FSTL1, FSTL4, FSTL5, Heart failure, Inflammation,
• MeSH
• biologické markery MeSH
• fibróza MeSH
• folistatin MeSH
• kardiovaskulární nemoci * MeSH
• lidé MeSH
• proteiny související s folistatinem * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• folistatin MeSH
• FSTL1 protein, human MeSH Prohlížeč
• proteiny související s folistatinem * MeSH

UNLABELLED: We describe the association of Becker muscular dystrophy (BMD) derived heart failure with the impairment of tissue homeostasis and remodeling capabilities of the affected heart tissue. We report that BMD heart failure is associated with a significantly decreased number of cardiovascular progenitor cells, reduced cardiac fibroblast migration, and ex vivo survival. BACKGROUND: Becker muscular dystrophy belongs to a class of genetically inherited dystrophin deficiencies. It affects male patients and results in progressive skeletal muscle degeneration and dilated cardiomyopathy leading to heart failure. It is a relatively mild form of dystrophin deficiency, which allows patients to be on a heart transplant list. In this unique situation, the explanted heart is a rare opportunity to study the degenerative process of dystrophin-deficient cardiac tissue. Heart tissue was excised, dissociated, and analyzed. The fractional content of c-kit+/CD45- cardiovascular progenitor cells (CVPCs) and cardiac fibroblast migration were compared to control samples of atrial tissue. Control tissue was obtained from the hearts of healthy organ donor's during heart transplantation procedures. RESULTS: We report significantly decreased CVPCs (c-kit+/CD45-) throughout the heart tissue of a BMD patient, and reduced numbers of phase-bright cells presenting c-kit positivity in the dystrophin-deficient cultured explants. In addition, ex vivo CVPCs survival and cardiac fibroblasts migration were significantly reduced, suggesting reduced homeostatic support and irreversible tissue remodeling. CONCLUSIONS: Our findings associate genetically derived heart failure in a dystrophin-deficient patient with decreased c-kit+/CD45- CVPCs and their resilience, possibly hinting at a lack of cardioprotective capability and/or reduced homeostatic support. This also correlates with reduced plasticity of the explanted cardiac tissue, related to the process of irreversible remodeling in the BMD patient's heart.

• Klíčová slova
• Becker muscular dystrophy, C-kit, Cardiomyopathy, Cardiovascular progenitor cells, Dystrophin, Heart failure,
• MeSH
• dilatační kardiomyopatie * MeSH
• Duchennova muskulární dystrofie * MeSH
• dystrofin MeSH
• kmenové buňky MeSH
• lidé MeSH
• myokard MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dystrofin MeSH