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1.
Kardiologiia ; 62(6): 15-22, 2022 Jun 30.
Artigo em Russo | MEDLINE | ID: mdl-35834337

RESUMO

Aim    To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods    This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results    The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, and cellular levels (r>0.3, р<0.05) and showed positive and negative correlations with PWV. The following blood plasma factors were selected as the markers of ageing: insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), and vascular endothelium adhesion molecule 1 (VCAM-1). A significant negative correlation between PWV and IGF-1 concentration was found. Among the tissue markers, P16INK, the key marker for tissue accumulation of senescent cells, predictably showed a positive correlation (r=0.394, p<0.05). A medium-strength correlation with parameters of the 96-h increment of mesenchymal stromal cells and fibroblasts and a weak correlation with IL-6 as a SASP (specific senescent-associated secretory phenotype) were noted. Results of the multifactorial linear regression analysis showed that the blood plasma marker, VCAM-1, and the cell marker, 96-h increment of fibroblasts, were associated with PWV regardless of the patient's age.Conclusion    Stiffness of great arteries as measured by PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.


Assuntos
Análise de Onda de Pulso , Rigidez Vascular , Animais , Biomarcadores , Senescência Celular , Feminino , Fator de Crescimento Insulin-Like I , Masculino , Molécula 1 de Adesão de Célula Vascular
2.
Bull Exp Biol Med ; 171(4): 523-531, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542758

RESUMO

Idiopathic pulmonary fibrosis can be caused by different factors, including accumulation of pathological extracellular matrix (ECM) with abnormal composition, stiffness, and architecture in the lung tissue. We studied the effect of ECM produced by lung fibroblasts of healthy mice or mice with bleomycin-induced pulmonary fibrosis on the process of endothelialto- mesenchymal transition, one of the main sources of effector myofibroblasts in fibrosis progression. Despite stimulation of spontaneous and TGFß-1-induced differentiation of fibroblasts into myofibroblasts by fibrotic ECM, the appearance of α-SMA, the main marker of myofibroblasts, and its integration in stress fibrils in endotheliocytes were not observed under similar conditions. However, the expression of transcription factors SNAI1 and SNAI2/Slug and the production of components of fibrotic ECM (specific EDA-fibronectin splice form and collagen type I) were increased in endotheliocytes cultured on fibrotic ECM. Endothelium also demonstrated increased cell velocity in the models of directed cell migration. These data indicate activation of the intermediate state of the endothelial-to-mesenchymal transition in endotheliocytes upon contact with fibrotic, but not normal stromal matrix. In combination with the complex microenvironment that develops during fibrosis progression, it can lead to the replenishment of myofibroblasts pool from the resident endothelium.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Matriz Extracelular/fisiologia , Fibrose Pulmonar/patologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/metabolismo , Matriz Extracelular Descelularizada/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibroblastos/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/fisiologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Alicerces Teciduais
3.
Biomed Pharmacother ; 109: 1428-1436, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551394

RESUMO

Male infertility represents a severe social and medical challenge. In recent years the progress in regenerative medicine promoted the development of novel options to overcome this medical condition. We are elaborating a promising approach to restore spermatogenesis using mesenchymal stromal cell (MSC) secretome components as a novel class of cell-free cell therapy medicinal products for regenerative medicine. However, the choice of the representative in vivo model of spermatogenesis failure to evaluate the effectiveness of regenerative drugs remains challenging. Using the rat model of bilateral abdominal cryptorchidism, we studied the contribution of MSC conditioned medium contained bioactive cell secreted products to the spermatogenesis recovery. The feasibility of this model to evaluate the drug-driven regenerative effects on spermatogenesis restoration after the injury was demonstrated. We revealed significant correlations between the extent of spermatogonial stem cell niche recovery, spermatozoa count and serum concentration of androgens as an indicator of Leydig cell function. The obtained results can be applied in preclinical studies to choose the proper criteria to appraise the specific activity of novel regenerative drugs developed for the treatment of non-obstructive spermatogenesis disorders.


Assuntos
Criptorquidismo/patologia , Células-Tronco Mesenquimais/patologia , Regeneração/fisiologia , Androgênios/metabolismo , Animais , Criptorquidismo/metabolismo , Meios de Cultivo Condicionados/metabolismo , Modelos Animais de Doenças , Humanos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Wistar , Medicina Regenerativa/métodos , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Espermatozoides/patologia
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