Progenitor cells from atria, ventricle and peripheral blood of the same patients exhibit functional differences associated with cardiac repair

Dixit, Priyadarshini; Donnelly, Hayden; Edamatsu, Midori; Galvin, Ivor F.; Bunton, Richard; Katare, Rajesh

doi:10.1016/j.ijcard.2016.11.178

Cited by 11 publications

(18 citation statements)

References 46 publications

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“…5a ) with no difference in CD105 population. Although CD105 is considered as the major CPC, our earlier studies showed the crucial role for CD90 in CPC migration [ 20 ]. Reduced CD90 in diabetic CPCs therefore suggest impaired migration in diabetic CPCs.…”

Section: Resultsmentioning

confidence: 99%

“…CPCs were isolated using our published protocol [ 20 ]. In brief, adipose tissue was removed from the RAA sample before the RAA was digested mechanically and chemically (2% collagenase II (Worthington Biochemical Corporation, USA).…”

Section: Methodsmentioning

confidence: 99%

“…To preserve their epigenetic memory, diabetic CPCs were continued to be cultured in the presence of high glucose (30 mM) throughout the experimental period. Purity of the cells was characterized using flow cytometry for the expression of CD90 and CD105 mesenchymal stem cell markers at the end of two weeks of culture, as described previously [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

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Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells

et al. 2018

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Increased apoptosis and premature cellular ageing of the diabetic heart underpin the development of diabetic heart disease. The molecular mechanisms underlying these pathologies are still unclear. Here we determined the role of pro-senescence microRNA (miR)-34a in accelerating the ageing of the diabetic heart. RT-PCR analysis showed a significant increase in the level of circulating miR-34a from early stages in asymptomatic type-2 diabetic individuals compared to non-diabetic controls. We also observed significant upregulation of miR-34a in the type-2 human diabetic heart suggesting circulating miR-34a may be cardiac in origin. Moreover, western blot analysis identified marked downregulation of the pro-survival protein sirtuin 1 (SIRT1), a direct target of miR-34a. Analysis of cultured human adult cardiomyocytes exposed to high glucose and cardiac progenitor cells (CPCs) isolated from the diabetic heart confirmed significant upregulation of miR-34a and downregulation of SIRT1, associated with a marked increase in pro-apoptotic caspase-3/7 activity. Although therapeutic inhibition of miR-34a activity restored SIRT1 expression in both cardiomyocytes and CPCs, p53 expression was further upregulated in cardiomyocytes but conversely downregulated in CPCs. In spite of increased p53, miR-34a inhibition significantly reduced high glucose induced apoptotic cell death in cardiomyocytes. However, this effect was not observed in CPCs, which in fact showed reduced proliferation following miR-34a inhibition. Taken together, our results demonstrate upregulation of miR-34a in the diabetic heart and in the circulation from an early stage of the disease. However, inhibition of miR-34a activity has differential effects depending on the cell type, thereby warranting the need to eliminate off-target effects when introducing miR-based therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells

et al. 2018

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“…S1C and S1D), suggesting that exogenous SP stimulates resident CPC accumulation into the RA of I/R-injured hearts. RA is known to be a good source of c-Kit + CPC [3,4]. We examined whether the up-regulation of stem cell markers in RA 1 day SP+I/R could be due to the increased c-Kit + CPC population.…”

Section: Resultsmentioning

confidence: 99%

Substance P enhances the local activation of NK1R-expressing c-Kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart

Jeong

Cheng

Lee

et al. 2020

Preprint

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Background: Localization of neurokinin 1 receptor (NK1R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK1R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n=22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP+I/R), and SP+I/R with 1 mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NK1R antagonist) (RP/SP+I/R). The left anterior descending coronary artery was occluded for 40 min followed by 1 day reperfusion with SP or SP+RP or without either. After 1 day, both atria and ventricles as well as the heart apexes were collected. Results: SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP+I/R rats via NK1R activation. In agreement with these observations, NK1R-expressing c-Kit+ Nkx2.5+GATA4+ cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA1 day SP+I/R approximately 2-fold increase more than RA1 day I/R. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NK1R antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit+ CPCs Conclusion: SP/NK1R might play a role as a key mediator involved in the cellular response to c-Kit+ CPC expansion in RA of the heart within 24 h after I/R.

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“…The frequency of CPCs is generally higher in the right atrium (RA) than in the left atrium (LA) and left ventricle (LV) [3]. A previous study compared the functional characteristics of RA CPCs, endothelial progenitor cells, and LV CPCs derived from the same patients (n = 14) [4]. RA CPCs showed greater expansion and migration potential compared to LV CPCs within the same patients [4].…”

Section: Introductionmentioning

confidence: 99%

Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart

Jeong

Cheng

Lee

et al. 2020

BMC Mol and Cell Biol

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Background: Localization of neurokinin 1 receptor (NK 1 R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK 1 R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n = 22 each); subjected to sham, ischemia/reperfusioninjury (I/R), I/R with 5 nmole/kg SP injection (SP + I/R), and SP + I/R with 1 mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NK 1 R antagonist) (RP/SP + I/R). The left anterior descending coronary artery was occluded for 40 min followed by 1 day reperfusion with SP or SP + RP or without either. After 1 day, both atria and ventricles as well as the heart apexes were collected. Results: SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP + I/R rats via NK 1 R activation. In agreement with these observations, NK 1 R-expressing c-Kit + Nkx2.5 + GATA4 + cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA 1 day SP + I/R approximately 2fold increase more than RA 1 day I/R. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NK 1 R antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit + CPCs. Conclusion: SP/NK 1 R might play a role as a key mediator involved in the cellular response to c-Kit + CPC expansion in RA of the heart within 24 h after I/R.

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Progenitor cells from atria, ventricle and peripheral blood of the same patients exhibit functional differences associated with cardiac repair

Cited by 11 publications

References 46 publications

Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells

Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells

Substance P enhances the local activation of NK1R-expressing c-Kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart

Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart

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