Dataset Information

Investigation of cardiac fibroblasts using myocardial slices.

ABSTRACT:

Aims

Cardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and cultured in vitro, CFs undergo rapid phenotypic changes including increased expression of ?-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli using in vitro cultured mouse, dog and human myocardial slices.

Methods and results

Unloading of myocardial slices induced CF proliferation without ?-SMA expression up to 7?days in culture. CFs migrating onto the culture plastic support or cultured on glass expressed ?SMA within 3?days. The cells on the slice remained ?SMA(-) despite transforming growth factor-? (20?ng/ml) or angiotensin II (200?µM) stimulation. When diastolic load was applied to myocardial slices using A-shaped stretchers, CF proliferation was significantly prevented at Days 3 and 7 (P < 0.001).

Conclusions

Myocardial slices allow the study of CFs in a multicellular environment and may be used to effectively study mechanisms of cardiac fibrosis and potential targets.

SUBMITTER: Perbellini F

PROVIDER: S-EPMC5852538 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Investigation of cardiac fibroblasts using myocardial slices.

Perbellini Filippo F Watson Samuel A SA Scigliano Martina M Alayoubi Samha S Tkach Sebastian S Bardi Ifigeneia I Quaife Nicholas N Kane Christopher C Dufton Neil P NP Simon André A Sikkel Markus B MB Faggian Giuseppe G Randi Anna M AM Gorelik Julia J Harding Sian E SE Terracciano Cesare M CM

Cardiovascular research 20180101 1

<h4>Aims</h4>Cardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and cultured in vitro, CFs undergo rapid phenotypic changes including increased expression of α-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli using in vitro cultured mouse, dog and human myocardial slices.<h4>Methods and results</h4>Unloading of myocardial slic ...[more]

PMID: 29016704

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Project description:Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients. Its pathogenesis involves inflammation and fibrosis that damages the heart tissue and impairs cardiac function. Interleukin (IL)-17, a pro-inflammatory cytokine that plays an important role in a variety of chronic inflammatory processes can serve as an attractive therapeutic target. Anthocyanin, a water-soluble natural pigment, possesses impressive anti-inflammatory activity. However, its role in DCM is unclear. Hence, we investigated the protective effect of anthocyanin on the cardiovascular complications of diabetes using a mouse type 1 diabetes mellitus model induced by streptozotocin. Cardiac function and structural alterations in diabetic mice were tested by echocardiography, hematoxylin and eosin staining, and Masson trichrome staining. Immunohistochemistry was performed to evaluate the distribution and deposition of IL-17 and collagen I and III from the left ventricular tissues of diabetic mice. Cell viability was measured using the methyl thiazolyl tetrazolium assay. Protein levels of IL-17, tumor necrosis factor α, IL-1β, and IL-6 were determined using enzyme-linked immunosorbent assay. IL-17 and collagen I and III were detected by western blotting and immunofluorescence, and their mRNA levels were quantified using quantitative reverse transcription PCR. We observed that anthocyanin lowered blood glucose, improved cardiac function, and alleviated inflammation and fibrosis in the heart tissue of diabetic mice. Meanwhile, anthocyanin reduced the expression of IL-17 in high-glucose-treated cardiac fibroblasts and exhibited an anti-inflammatory effect. Deposition of collagen I and III was also decreased by anthocyanin, suggesting that anthocyanin contributes to alleviating myocardial fibrosis. In summary, anthocyanin could protect cardiac function and inhibit IL-17-related inflammation and fibrosis, which indicates its therapeutic potential in the treatment of diabetes mellitus-related complications.

Dataset Information

Investigation of cardiac fibroblasts using myocardial slices.

Aims

Methods and results

Conclusions

Publications

Investigation of cardiac fibroblasts using myocardial slices.

Similar Datasets

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