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Re-modelling 'hostile' milieu of diseased myocardium via paracrine function of transplanted cells or relaxin.

Du XJ - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: While the approaches of regenerating cardiac muscle remain undetermined, recent evidence indicates that paracrine function of transplanted cells contributes significantly to the beneficial effects of cell therapy.Combination of such paracrine function of grafted cells with extracellular matrix remodelling by relaxin represents a promising complement to cell-based therapy for cardiac repair and muscle regeneration.

View Article: PubMed Central - PubMed

Affiliation: Experimental Cardiology Laboratory, Baker Heart Research Institute, Melbourne, Australia. xiaojun.du@baker.edu.au

ABSTRACT
While the approaches of regenerating cardiac muscle remain undetermined, recent evidence indicates that paracrine function of transplanted cells contributes significantly to the beneficial effects of cell therapy. Combination of such paracrine function of grafted cells with extracellular matrix remodelling by relaxin represents a promising complement to cell-based therapy for cardiac repair and muscle regeneration.

Show MeSH

Related in: MedlinePlus

Recent studies have revealed multiple cardiac actions of the peptide hormone relaxin, including anti-apoptosis, pro-angiogenesis and anti-fibrosis. These actions are expected to be invaluable in overcoming major problems in the setting of cell-based therapy of heart disease. PI3K, phosphatidylinositol 3-kinase; VEGF, vascular endothelial growth factor; NOS, nitric oxide synthase; MMPs, matrix metalloproteinases.
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fig01: Recent studies have revealed multiple cardiac actions of the peptide hormone relaxin, including anti-apoptosis, pro-angiogenesis and anti-fibrosis. These actions are expected to be invaluable in overcoming major problems in the setting of cell-based therapy of heart disease. PI3K, phosphatidylinositol 3-kinase; VEGF, vascular endothelial growth factor; NOS, nitric oxide synthase; MMPs, matrix metalloproteinases.

Mentions: The finding of a better efficacy by myoblasts pre-infected with relaxin gene is extremely interesting. As a peptide hormone known to induce ECM re-mod-elling in the reproductive tissues for many decades, recent findings strongly indicate relaxin as a promising agent for heart disease therapy [11]. Well-documented cardiac protective actions of relaxin include anti-fibrosis [12, 13], anti-oxidative stress [14], anti-apoptosis [14, 15] and vasodilation via nitric oxide synthase (NOS)/nitric oxide signalling [16]. In cultured cardiomyocytes, relaxin protects cells against oxidative stress-induced apoptosis by activating pro-survival molecules like phosphoinositide 3-kinase (PI3K)/Akt, ERK and Bcl-2 [15]. These actions might underlie relaxin's potent protection against myocar-dial injury in vivo, seen in a porcine model of acute MI [14]. Pro-angiogenic action of relaxin has only been reported in skin wound, cancer or reproductive tissues [11, 17, 18]. The anti-fibrotic effect of relaxin is attributable to its multiple actions by which it inhibits activation and proliferation of fibroblasts and promotes collagen degradation by up-regulating expression of MMPs together with down-regulation of certain subtypes of tissue inhibitors of metallopro-teinases (TIMPs) [11]. In settings of heart disease and cell therapy, combination of these actions would certainly be desirable (Fig. 1). Interestingly, all these known actions of relaxin have been observed in the porcine infarcted cardiac tissue [9]. It is known that regional formation of a number of cytokines, chemokines, growth factors and MMPs are critical for stem cell homing, migration, myocyte-lineage formation and proliferation [19]. In addition, studies in non-cardiac tissues have revealed that relaxin is able to synergistically activate the insulin-like growth factor (IGF1) signalling [21]. While the importance of IGF1/ phosphatidylinositol 3-kinase (PI3K) pathway in the outcome of myocardial regeneration has been demonstrated [6], the possibility that relaxin interacts with IGF1/PI3K signalling in cardiac cell therapy warrants further investigation.


Re-modelling 'hostile' milieu of diseased myocardium via paracrine function of transplanted cells or relaxin.

Du XJ - J. Cell. Mol. Med. (2007 Sep-Oct)

Recent studies have revealed multiple cardiac actions of the peptide hormone relaxin, including anti-apoptosis, pro-angiogenesis and anti-fibrosis. These actions are expected to be invaluable in overcoming major problems in the setting of cell-based therapy of heart disease. PI3K, phosphatidylinositol 3-kinase; VEGF, vascular endothelial growth factor; NOS, nitric oxide synthase; MMPs, matrix metalloproteinases.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401275&req=5

fig01: Recent studies have revealed multiple cardiac actions of the peptide hormone relaxin, including anti-apoptosis, pro-angiogenesis and anti-fibrosis. These actions are expected to be invaluable in overcoming major problems in the setting of cell-based therapy of heart disease. PI3K, phosphatidylinositol 3-kinase; VEGF, vascular endothelial growth factor; NOS, nitric oxide synthase; MMPs, matrix metalloproteinases.
Mentions: The finding of a better efficacy by myoblasts pre-infected with relaxin gene is extremely interesting. As a peptide hormone known to induce ECM re-mod-elling in the reproductive tissues for many decades, recent findings strongly indicate relaxin as a promising agent for heart disease therapy [11]. Well-documented cardiac protective actions of relaxin include anti-fibrosis [12, 13], anti-oxidative stress [14], anti-apoptosis [14, 15] and vasodilation via nitric oxide synthase (NOS)/nitric oxide signalling [16]. In cultured cardiomyocytes, relaxin protects cells against oxidative stress-induced apoptosis by activating pro-survival molecules like phosphoinositide 3-kinase (PI3K)/Akt, ERK and Bcl-2 [15]. These actions might underlie relaxin's potent protection against myocar-dial injury in vivo, seen in a porcine model of acute MI [14]. Pro-angiogenic action of relaxin has only been reported in skin wound, cancer or reproductive tissues [11, 17, 18]. The anti-fibrotic effect of relaxin is attributable to its multiple actions by which it inhibits activation and proliferation of fibroblasts and promotes collagen degradation by up-regulating expression of MMPs together with down-regulation of certain subtypes of tissue inhibitors of metallopro-teinases (TIMPs) [11]. In settings of heart disease and cell therapy, combination of these actions would certainly be desirable (Fig. 1). Interestingly, all these known actions of relaxin have been observed in the porcine infarcted cardiac tissue [9]. It is known that regional formation of a number of cytokines, chemokines, growth factors and MMPs are critical for stem cell homing, migration, myocyte-lineage formation and proliferation [19]. In addition, studies in non-cardiac tissues have revealed that relaxin is able to synergistically activate the insulin-like growth factor (IGF1) signalling [21]. While the importance of IGF1/ phosphatidylinositol 3-kinase (PI3K) pathway in the outcome of myocardial regeneration has been demonstrated [6], the possibility that relaxin interacts with IGF1/PI3K signalling in cardiac cell therapy warrants further investigation.

Bottom Line: While the approaches of regenerating cardiac muscle remain undetermined, recent evidence indicates that paracrine function of transplanted cells contributes significantly to the beneficial effects of cell therapy.Combination of such paracrine function of grafted cells with extracellular matrix remodelling by relaxin represents a promising complement to cell-based therapy for cardiac repair and muscle regeneration.

View Article: PubMed Central - PubMed

Affiliation: Experimental Cardiology Laboratory, Baker Heart Research Institute, Melbourne, Australia. xiaojun.du@baker.edu.au

ABSTRACT
While the approaches of regenerating cardiac muscle remain undetermined, recent evidence indicates that paracrine function of transplanted cells contributes significantly to the beneficial effects of cell therapy. Combination of such paracrine function of grafted cells with extracellular matrix remodelling by relaxin represents a promising complement to cell-based therapy for cardiac repair and muscle regeneration.

Show MeSH
Related in: MedlinePlus