Impact of type 1 diabetes on cardiac fibroblast activation: enhanced cell cycle progression and reduced myofibroblast content in diabetic myocardium

Shamhart, Patricia E.; Luther, Daniel J.; Hodson, Ben R.; Koshy, John C.; Ohanyan, Vahagn; Meszaros, J. Gary

doi:10.1152/ajpendo.00327.2009

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…When superimposed on MI, chronic inflammation prolongs wound healing and generates a potentially inadequate scar. Our findings are consistent with studies in early-stage diabetic hearts, where cardiac fibroblasts were highly proliferative and proinflammatory, resulting in compromised wound healing and increased LV dilation (39). Understanding how chronic inflammation alters cardiac wound healing provides insight into how to limit post-MI progression to congestive heart failure.…”

Section: Discussionsupporting

confidence: 89%

Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing

DeLeon‐Pennell

Iyer²,

Ero³

et al. 2017

JCI Insight

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Section: Discussionsupporting

confidence: 89%

Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing

DeLeon‐Pennell

Iyer²,

Ero³

et al. 2017

JCI Insight

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“…Our data revealed that T2DM CF exhibit similar proliferation rates to ND cells, which contrasts with previous studies using CF from rat models of Type 1 [35] and Type 2 [17] diabetes. Such discrepancies are likely to be multi-factorial and include inter-species variation, differences in duration of hyperglycaemia or age differences.…”

Section: Discussioncontrasting

confidence: 99%

Investigating inherent functional differences between human cardiac fibroblasts cultured from nondiabetic and Type 2 diabetic donors

Sedgwick

Riches

Bageghni

et al. 2014

Cardiovascular Pathology

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Introduction: Type 2 diabetes mellitus (T2DM) promotes adverse myocardial remodelling and increased risk of heart failure; effects that can occur independently of hypertension or coronary artery disease. As cardiac fibroblasts (CF) are key effectors of myocardial remodelling, we investigated whether inherent phenotypic differences exist in CF derived from T2DM donors compared with cells from non-diabetic (ND) donors. Methods:Cell morphology (cell area), proliferation (cell counting over 7-day period), insulin signalling (phospho-Akt and phospho-ERK Western blotting) and mRNA expression of key remodelling genes (real-time RT-PCR) were compared in CF cultured from atrial tissue from 14 ND and 12 T2DM donors undergoing elective coronary artery bypass surgery. Results:The major finding was that type I collagen (COL1A1) mRNA levels were significantly elevated by 2-fold in cells derived from T2DM donors compared with those from ND donors; changes reflected at the protein level. T2DM cells had similar proliferation rates but a greater variation in cell size and a trend towards increased cell area compared with ND cells. Insulininduced Akt and ERK phosphorylation were similar in the two cohorts of cells. Conclusion:CF from T2DM individuals possess an inherent pro-fibrotic phenotype that may help to explain the augmented cardiac fibrosis observed in diabetic patients. Mini SummaryWe investigated whether inherent phenotypic differences exist between cardiac fibroblasts cultured from donors with or without Type 2 diabetes. Cell morphology, proliferation, insulin signalling and gene expression were compared between multiple cell populations. The major finding was that type I collagen levels were elevated in fibroblasts from diabetic donors, which may help explain the augmented cardiac fibrosis observed with diabetes.

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“…We have previously reported that cardiac fibroblasts isolated directly from the diabetic myocardium were more proliferative than fibroblasts from the healthy, control myocardium (Shamhart et al, 2009). In fact, high glucose has been found to stimulate cardiac fibroblast proliferation in vitro but as described for migration, different labs utilized a unique cell culture system (Asbun and Villarreal, 2006; Neumann et al, 2002), therefore we sought to establish the impact of hyperglycemia on fibroblast proliferation in our system.…”

Section: Discussionmentioning

confidence: 99%

“…Cell lysates were collected as previously described by our lab (Olson et al, 2005; Olson et al, 2008; Shamhart et al, 2009). Protein levels were quantified with the BCA method (Pierce) and equal amount of protein were mixed with 2X sample buffer (100mM Tris base, 20% glycerol, 2% SDS, and 0.01% bromophenol blue) and boiled for 5 minutes.…”

Section: Methodsmentioning

confidence: 99%

Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts

Shamhart

Luther

Adapala

et al. 2014

Can. J. Physiol. Pharmacol.

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Diabetes is an independent risk factor of cardiovascular disease that can eventually cause cardiomyopathy and heart failure. Cardiac fibroblasts (CF) are the critical mediators of physiological and pathological cardiac remodeling, however, the effects of hyperglycemia on cardiac fibroblast function and differentiation is not well known. Here, we performed a comprehensive investigation on the effects of hyperglycemia on cardiac fibroblasts and show that hyperglycemia enhances cardiac fibroblast function and differentiation. We found that high glucose treatment increased collagen I, III and VI gene expression in rat adult cardiac fibroblasts. Interestingly, hyperglycemia increased CF migration and proliferation which is augmented by collagen I and III. Surprisingly, we found that short term hyperglycemia transiently inhibited ERK1/2 activation but increased AKT phosphorylation. Finally, high glucose treatment increased spontaneous differentiation of cardiac fibroblasts to myofibroblasts with increasing passage compared to low glucose. Taken together, these findings suggest that hyperglycemia induces cardiac fibrosis by modulating collagen expression, migration, proliferation and differentiation of cardiac fibroblasts.

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Impact of type 1 diabetes on cardiac fibroblast activation: enhanced cell cycle progression and reduced myofibroblast content in diabetic myocardium

Abstract: Shamhart PE, Luther DJ, Hodson BR, Koshy JC, Ohanyan V, Meszaros JG. Impact of type 1 diabetes on cardiac fibroblast activation: enhanced cell cycle progression and reduced myofibroblast content in diabetic myocardium.

Cited by 17 publications

References 32 publications

Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing

Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing

Investigating inherent functional differences between human cardiac fibroblasts cultured from nondiabetic and Type 2 diabetic donors

Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts

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