Limits...
Fibroblast growth factor-9 enhances M2 macrophage differentiation and attenuates adverse cardiac remodeling in the infarcted diabetic heart.

Singla DK, Singla RD, Abdelli LS, Glass C - PLoS ONE (2015)

Bottom Line: Inflammation has been implicated as a perpetrator of diabetes and its associated complications.MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs.MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs.

View Article: PubMed Central - PubMed

Affiliation: Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.

ABSTRACT
Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean ± SEM; MI: 2.02% ± 0.23% vs. Sham 0.75% ± 0.07%; p<0.05) and associated pro-inflammatory cytokines (TNF-α, MCP-1, and IL-6), adverse cardiac remodeling (Mean ± SEM; MI: 33% ± 3.04% vs. Sham 2.2% ± 0.33%; p<0.05), and left ventricular dysfunction (Mean ± SEM; MI: 35.4% ± 1.25% vs. Sham 49.19% ± 1.07%; p<0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean ± SEM; MI+FGF-9: 1.39% ± 0.1% vs. MI: 2.02% ± 0.23%; p<0.05), increased M2 macrophage differentiation (Mean ± SEM; MI+FGF-9: 4.82% ± 0.86% vs. MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs. MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs. MI: 35.4% ± 1.25%; p<0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to mediate monocyte to M2 differentiation and confer cardiac protection in the post-MI diabetic heart.

No MeSH data available.


Related in: MedlinePlus

Exogenous FGF-9 Treatment Improves Cardiac Function Following MI.2 weeks post MI, 2D transthoracic echocardiography was performed on control and experimental animals. All mean data for each quantified measurement are presented in A. Quantitative analyses are shown for left ventricular internal dimension-diastole (LVIDd) (B), left ventricular internal dimension-systole (LVIDs) (C), fractional shortening (FS) (D), left ventricular volume at end diastole (EDV) (E), left ventricular volume at end systole (ESV) (F), and ejection fraction (EF) (G). n = 5 animals/group. *p<0.05 vs. sham and #p<0.05 vs. MI.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4359124&req=5

pone.0120739.g006: Exogenous FGF-9 Treatment Improves Cardiac Function Following MI.2 weeks post MI, 2D transthoracic echocardiography was performed on control and experimental animals. All mean data for each quantified measurement are presented in A. Quantitative analyses are shown for left ventricular internal dimension-diastole (LVIDd) (B), left ventricular internal dimension-systole (LVIDs) (C), fractional shortening (FS) (D), left ventricular volume at end diastole (EDV) (E), left ventricular volume at end systole (ESV) (F), and ejection fraction (EF) (G). n = 5 animals/group. *p<0.05 vs. sham and #p<0.05 vs. MI.

Mentions: To determine the impact of FGF-9 on left ventricular function post-MI, 2D transthoracic echocardiography was performed on all control and experimental mice. All raw data is provided in Fig. 6A. Two weeks post-MI, EDV and ESV were significantly increased (p<0.05, Fig. 6E and F, resepctively), whereas FS and EF were significantly diminished compared to the sham operated mice (p<0.05, Fig. 6D and G, resepctively). Notably, LVIDd, LVIDs, EDV, and ESV were significantly decreased (p<0.05, Fig. 6B, C, E, and F, resepctively) and FS amd EF were significantly improved (p<0.05, Fig. 6D and G, resepctively) in the FGF-9 treated mice relative to the MI alone mice. All echocardiographic data, taken into consideration, suggest FGF-9 preserves systolic and diastolic function and protects the diabetic heart from cardiac dysfunction consequent to MI.


Fibroblast growth factor-9 enhances M2 macrophage differentiation and attenuates adverse cardiac remodeling in the infarcted diabetic heart.

Singla DK, Singla RD, Abdelli LS, Glass C - PLoS ONE (2015)

Exogenous FGF-9 Treatment Improves Cardiac Function Following MI.2 weeks post MI, 2D transthoracic echocardiography was performed on control and experimental animals. All mean data for each quantified measurement are presented in A. Quantitative analyses are shown for left ventricular internal dimension-diastole (LVIDd) (B), left ventricular internal dimension-systole (LVIDs) (C), fractional shortening (FS) (D), left ventricular volume at end diastole (EDV) (E), left ventricular volume at end systole (ESV) (F), and ejection fraction (EF) (G). n = 5 animals/group. *p<0.05 vs. sham and #p<0.05 vs. MI.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359124&req=5

pone.0120739.g006: Exogenous FGF-9 Treatment Improves Cardiac Function Following MI.2 weeks post MI, 2D transthoracic echocardiography was performed on control and experimental animals. All mean data for each quantified measurement are presented in A. Quantitative analyses are shown for left ventricular internal dimension-diastole (LVIDd) (B), left ventricular internal dimension-systole (LVIDs) (C), fractional shortening (FS) (D), left ventricular volume at end diastole (EDV) (E), left ventricular volume at end systole (ESV) (F), and ejection fraction (EF) (G). n = 5 animals/group. *p<0.05 vs. sham and #p<0.05 vs. MI.
Mentions: To determine the impact of FGF-9 on left ventricular function post-MI, 2D transthoracic echocardiography was performed on all control and experimental mice. All raw data is provided in Fig. 6A. Two weeks post-MI, EDV and ESV were significantly increased (p<0.05, Fig. 6E and F, resepctively), whereas FS and EF were significantly diminished compared to the sham operated mice (p<0.05, Fig. 6D and G, resepctively). Notably, LVIDd, LVIDs, EDV, and ESV were significantly decreased (p<0.05, Fig. 6B, C, E, and F, resepctively) and FS amd EF were significantly improved (p<0.05, Fig. 6D and G, resepctively) in the FGF-9 treated mice relative to the MI alone mice. All echocardiographic data, taken into consideration, suggest FGF-9 preserves systolic and diastolic function and protects the diabetic heart from cardiac dysfunction consequent to MI.

Bottom Line: Inflammation has been implicated as a perpetrator of diabetes and its associated complications.MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs.MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs.

View Article: PubMed Central - PubMed

Affiliation: Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.

ABSTRACT
Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean ± SEM; MI: 2.02% ± 0.23% vs. Sham 0.75% ± 0.07%; p<0.05) and associated pro-inflammatory cytokines (TNF-α, MCP-1, and IL-6), adverse cardiac remodeling (Mean ± SEM; MI: 33% ± 3.04% vs. Sham 2.2% ± 0.33%; p<0.05), and left ventricular dysfunction (Mean ± SEM; MI: 35.4% ± 1.25% vs. Sham 49.19% ± 1.07%; p<0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean ± SEM; MI+FGF-9: 1.39% ± 0.1% vs. MI: 2.02% ± 0.23%; p<0.05), increased M2 macrophage differentiation (Mean ± SEM; MI+FGF-9: 4.82% ± 0.86% vs. MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs. MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs. MI: 35.4% ± 1.25%; p<0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to mediate monocyte to M2 differentiation and confer cardiac protection in the post-MI diabetic heart.

No MeSH data available.


Related in: MedlinePlus