Pathophysiological aldosterone levels modify the secretory activity of cardiac progenitor cells

Wenzel, Kristin; Samal, Rasmita; Hammer, Elke; Dhople, Vishnu M.; Groß, Stefan; Völker, Uwe; Felix, Stephan B.; Könemann, Stephanie

doi:10.1016/j.mce.2016.10.009

Cited by 3 publications

(8 citation statements)

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“…It is generally believed that the ambience of endogenous cardiac cells is modified during cardiac injury (Pereira, Carvalho, Karp, & Ferreira, 2011). We have recently shown that pathophysiological levels of aldosterone modulate the secretory activity of Sca-1 + cells promoting cell migration (Wenzel et al, 2017). In the current study, we were factors such as CTGF and MIME known to mediate cardiac protection and/repair after myocardial infarction (Ahmed et al, 2011;Van Aelst et al, 2015), as well as cytokines such as CSF1, MYDGF known to contribute to the regulation of stem cell fate and maintenance of cardiac function (Korf-Klingebiel et al, 2015;Leblond et al, 2015) were higher abundant in Cyc CM than in Wt CM.…”

Section: Discussionmentioning

confidence: 59%

“…We have recently shown that Sca-1 + cells are tolerant to serum-free conditions for up to 24 hr. At later time-points cellular stress was induced equivalent to that caused by pathophysiological aldosterone levels (Wenzel et al, 2017), which is why we chose to characterize the secretome within 24 hr. Moreover, distinguishing authentic secreted proteins has been the biggest challenge in secretome-based studies.…”

Section: Discussionmentioning

confidence: 99%

“…Conditioned medium (CM) was generated from cultured Sca-1 cells as described previously (Wenzel et al, 2017). Briefly, Sca-1 + cells were cultured in regular growth medium containing 20% FBS until they reached 80% confluency.…”

Section: Preparation Of Conditioned Mediamentioning

confidence: 99%

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Global secretome analysis of resident cardiac progenitor cells from wild‐type and transgenic heart failure mice: Why ambience matters

Samal

Sappa

Salazar

et al. 2018

Journal Cellular Physiology

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Resident cardiac progenitor cells (CPCs) have gained attention in cardiac regenerative medicine primarily due to their paracrine activity. In our current study we determined the role of pathological conditions such as heart failure on the autocrine‐paracrine action of stem cell antigen‐1 (Sca‐1) expressing CPC. This comparative secretome profiling of Sca‐1+ cells derived from transgenic heart failure (αMHC–cyclin‐T1/Gαq overexpression [Cyc] cells) versus healthy (wild‐type [Wt] cells) mice, achieved via mass‐spectrometric quantification, enabled the identification of over 700 proteins. Our results demonstrate that the heart failure milieu caused a 2‐fold enrichment of extracellular matrix proteins (ECM) like biglycan, versican, collagen XII, and angiogenic factors like heparan sulfate proteoglycan 2, plasminogen activator inhibitor 1 in the secretome. We further elucidated the direct influence of the secretome on the functional behavior of Sca‐1 + cells via in vitro tube forming assay. Secreted factors present in the diseased milieu induced tube formation in Cyc cells (1.7‐fold; p < 0.01) when compared with Wt cells after 24 hr of exposure. The presence of conditioned media moderately increased the proliferation of Cyc cells but had a more pronounced effect on Wt cells. Overall, these findings revealed global modifications in the secretory activity of adult Sca‐1 + cells in the heart failure milieu. The secretion of ECM proteins and angiogenic factors, which are crucial for cardiac remodeling and recovery, was notably enriched in the supernatant of Cyc cells. Thus, during heart failure the microenvironment of Sca‐1 + cells might favor angiogenesis and proliferation suggesting their potential to recover the damaged heart.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

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Global secretome analysis of resident cardiac progenitor cells from wild‐type and transgenic heart failure mice: Why ambience matters

Samal

Sappa

Salazar

et al. 2018

Journal Cellular Physiology

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“…MR antagonists such as eplerenone or spironolactone could increase the number and improve the function of EPCs . Instead, MR activation could also improve migration and modify the secretory activity of cardiac progenitor cells . The discrepancy might be because of different stem cell types and study design (in vitro vs in vivo).…”

Section: Discussionmentioning

confidence: 99%

“…21,41 Instead, MR activation could also improve migration and modify the secretory activity of cardiac progenitor cells. 42,43 The discrepancy might be because of different stem cell types and study design (in vitro vs in vivo). Furthermore, short-term as opposed to chronic exposure to MR activation might also explain the inconsistency among studies.…”

Section: Depletion Of Mr Promoted Angiogenesismentioning

confidence: 99%

Mineralocorticoid receptor deficiency improves the therapeutic effects of mesenchymal stem cells for myocardial infarction via enhanced cell survival

Xie¹,

Shen

Chen

et al. 2018

J Cellular Molecular Medi

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The poor survival of stem cells seriously limits their therapeutic efficacy for myocardial infarction (MI). Mineralocorticoid receptor (MR) activation plays an important role in the pathogenesis of multiple cardiovascular diseases. Here, we examined whether MR silencing in bone marrow derived mesenchymal stem cells (MSCs) could improve MSCs’ survival and enhance their cardioprotective effects in MI. MSCs from male Sprague‐Dawley rats were transfected with adenoviral small interfering RNA to silence MR (siRNA‐MR). MR silencing decreased hypoxia‐induced MSCs’ apoptosis, as demonstrated by Annexin V/7‐AAD staining. The mechanisms contributing to the beneficial effects of MR depletion were associated with inhibiting intracellular reactive oxygen species production and increased Bcl‐2/Bax ratio. In vivo study, 1 × 106 of MSCs with or without siRNA‐MR were injected into rat hearts immediately after MI. Depletion of MR could improve the MSCs’ survival significantly in infarcted myocardium, associated with more cardiac function improvement and smaller infarct size. Capillary density were also significantly higher in siRNA group with increased expression of vascular endothelial growth factor. Our study demonstrated that silencing MR promoted MSCs’ survival and repair efficacy in ischaemic hearts. MR might be a potential target for enhancing the efficacy of cell therapy in ischaemic heart disease.

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Cardioprotective effect of the secretome of Sca-1+ and Sca-1− cells in heart failure: not equal, but equally important?

Könemann

Sartori

Groß

et al. 2019

Cardiovascular Research

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Aims Both progenitor and differentiated cells were previously shown to secrete cardioprotective substances, but so far there has been no direct comparison of the paracrine effects of the two cell types on heart failure. The study sought to compare the paracrine effect of selected progenitors and the corresponding non-progenitor mononuclear cardiac cells on the cardiac function of transgenic heart failure mice. In addition, we aimed to further enhance the paracrine effect of the cells via pretreatment with the heart failure mediator aldosterone. Methods and results Transgenic heart failure mice were injected with the supernatant of murine cardiac stem cell antigen-1 positive (Sca-1+) and negative (Sca-1−) cells with or without aldosterone pretreatment. Cardiac function was determined using small animal magnetic resonance imaging. In addition, heart failure markers were determined using enzyme-linked immunosorbent assay, RT–PCR, and bead-based multiplexing assay. While only the secretome of aldosterone pretreated Sca-1+ cells led to a significant improvement in cardiac function, N-terminal pro brain natriuretic peptide plasma levels were significantly lower and galectin-1 levels significantly higher in mice that were treated with either kind of secretome compared with untreated controls. Conclusion In this first direct comparison of the paracrine effects of progenitor cells and a heterogeneous population of mononuclear cardiac cells the supernatants of both cell types showed cardioprotective properties which might be of great relevance for endogenous repair. During heart failure raised aldosterone levels might further increase the paracrine effect of progenitor cells.

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Pathophysiological aldosterone levels modify the secretory activity of cardiac progenitor cells

Cited by 3 publications

References 59 publications

Global secretome analysis of resident cardiac progenitor cells from wild‐type and transgenic heart failure mice: Why ambience matters

Global secretome analysis of resident cardiac progenitor cells from wild‐type and transgenic heart failure mice: Why ambience matters

Mineralocorticoid receptor deficiency improves the therapeutic effects of mesenchymal stem cells for myocardial infarction via enhanced cell survival

Cardioprotective effect of the secretome of Sca-1+ and Sca-1− cells in heart failure: not equal, but equally important?

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