Changes in the number of mast cells, expression of fibroblast growth factor-2 and extent of interstitial fibrosis in established and advanced hypertensive heart disease

Kotov, Georgi; Landzhov, Boycho; Stamenov, Nikola; Stanchev, Stancho; Iliev, Alexandar

doi:10.1016/j.aanat.2020.151564

Cited by 16 publications

(15 citation statements)

References 53 publications

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“…However, involvement of mast cells in the development of adverse RV remodeling remains largely unexplored. Interestingly, increased mast cells numbers along with increased myocardial fibrosis have recently been found in right ventricles of rats spontaneously developing systemic hypertension [9]. Furthermore, we have demonstrated increased accumulation and activation of mast cells in pressure-overloaded right ventricles in mice subjected to sustained pressure overload [10].…”

Section: Introductionsupporting

confidence: 58%

Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice

Sydykov

Luitel

Mamazhakypov

et al. 2020

IJMS

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Although the response of the right ventricle (RV) to the increased afterload is an important determinant of the patient outcome, very little is known about the underlying mechanisms. Mast cells have been implicated in the pathogenesis of left ventricular maladaptive remodeling and failure. However, the role of mast cells in RV remodeling remains unexplored. We subjected mast cell-deficient WBB6F1-KitW/W-v (KitW/KitW-v) mice and their mast cell-sufficient littermate controls (MC+/+) to pulmonary artery banding (PAB). PAB led to RV dilatation, extensive myocardial fibrosis, and RV dysfunction in MC+/+ mice. In PAB KitW/KitW-v mice, RV remodeling was characterized by minimal RV chamber dilatation and preserved RV function. We further administered to C57Bl/6J mice either placebo or cromolyn treatment starting from day 1 or 7 days after PAB surgery to test whether mast cells stabilizing drugs can prevent or reverse maladaptive RV remodeling. Both preventive and therapeutic cromolyn applications significantly attenuated RV dilatation and improved RV function. Our study establishes a previously undescribed role of mast cells in pressure overload-induced adverse RV remodeling. Mast cells may thus represent an interesting target for the development of a new therapeutic approach directed specifically at the heart.

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Section: Introductionsupporting

confidence: 58%

Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice

Sydykov

Luitel

Mamazhakypov

et al. 2020

IJMS

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“…Based on our results it seems that chymase does not play any significant role in the developmental phase of hypertension, since no blood pressure or any other change was observed after chymase inhibition (similarly after chymostatin and rapeseedderived peptides). This is somewhat surprising, considering previous reports suggesting the important role of mast cells, the main source of chymase, in tissue fibrosis (Kotov et al, 2020). Possibly, mast cells-related tissue remodeling might be more pronounced in more advanced hypertensive heart disease.…”

Section: Rapeseed-derived Peptidesmentioning

confidence: 74%

Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats

et al. 2021

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The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY. These simple and easy to obtain peptides not only block chymase, but also possess weak activity to inhibit ACE. This is a first attempt to evaluate the impact of chronic administration of selected inhibitors on blood pressure of SHR in two phases of hypertension. Male SHR (6 or 16 weeks old) were treated daily for two weeks with chymostatin (CH; 2 mg/kg/day), the peptides VWIS (12.5 mg/kg/day) or RIY (7.5 mg/kg/day); control groups received chymostatin solvent (0.15% DMSO in saline) or peptide solvent (saline). The substances were administered intravenously to conscious animals via a chronically cannulated femoral vein. Systolic blood pressure (SBP) was measured by telemetry. Metabolic parameters were measured weekly, and tissue samples were harvested after two weeks of treatment. None of the administered chymase inhibitors affected the development of hypertension in young rats. Only RIY exhibited beneficial properties when administered in the established phase of hypertension: SBP decreased from 165 ± 10 to 157 ± 7 mmHg while the excretion of nitric oxide metabolites increased significantly. The glomerulosclerosis index was lower after RIY treatment in both age groups (significant only in young rats 0.29 ± 0.05 vs 0.48 ± 0.04 in the control group; p < 0.05). Hence, it seems that peptide RIY exhibits some positive effect on renal morphology. The results obtained suggest that the peptide RIY may be a useful tool in the treatment of hypertension, especially in cases when ACE inhibitors are not effective.

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“…A similar interaction between FGF2 and ERK1/2 in cardiac fibroblasts plays a role in the development of lipopolysaccharide (LPS)-triggered cardiac adverse events, leading to fibrosis and heart failure ( Chen et al, 2019 ). Along with an elevated number of cardiac mast cells in both ventricles under hypertrophic conditions, overexpression of Fgf2 may denote its pro-fibrotic role in the progress of myocardial fibrosis ( Kotov et al, 2020 ).…”

Section: Roles Of Fgf In Cardiac Pathophysiology and Repairmentioning

confidence: 99%

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

Khosravi

Ahmadvand

Bellusci

et al. 2021

Front. Cell Dev. Biol.

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The current focus on cardiovascular research reflects society’s concerns regarding the alarming incidence of cardiac-related diseases and mortality in the industrialized world and, notably, an urgent need to combat them by more efficient therapies. To pursue these therapeutic approaches, a comprehensive understanding of the mechanism of action for multifunctional fibroblast growth factor (FGF) signaling in the biology of the heart is a matter of high importance. The roles of FGFs in heart development range from outflow tract formation to the proliferation of cardiomyocytes and the formation of heart chambers. In the context of cardiac regeneration, FGFs 1, 2, 9, 16, 19, and 21 mediate adaptive responses including restoration of cardiac contracting rate after myocardial infarction and reduction of myocardial infarct size. However, cardiac complications in human diseases are correlated with pathogenic effects of FGF ligands and/or FGF signaling impairment. FGFs 2 and 23 are involved in maladaptive responses such as cardiac hypertrophic, fibrotic responses and heart failure. Among FGFs with known causative (FGFs 2, 21, and 23) or protective (FGFs 2, 15/19, 16, and 21) roles in cardiac diseases, FGFs 15/19, 21, and 23 display diagnostic potential. The effective role of FGFs on the induction of progenitor stem cells to cardiac cells during development has been employed to boost the limited capacity of postnatal cardiac repair. To renew or replenish damaged cardiomyocytes, FGFs 1, 2, 10, and 16 were tested in (induced-) pluripotent stem cell-based approaches and for stimulation of cell cycle re-entry in adult cardiomyocytes. This review will shed light on the wide range of beneficiary and detrimental actions mediated by FGF ligands and their receptors in the heart, which may open new therapeutic avenues for ameliorating cardiac complications.

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Changes in the number of mast cells, expression of fibroblast growth factor-2 and extent of interstitial fibrosis in established and advanced hypertensive heart disease

Cited by 16 publications

References 53 publications

Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice

Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice

Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

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