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Catestatin improves post-ischemic left ventricular function and decreases ischemia/reperfusion injury in heart.

Penna C, Alloatti G, Gallo MP, Cerra MC, Levi R, Tullio F, Bassino E, Dolgetta S, Mahata SK, Tota B, Pagliaro P - Cell. Mol. Neurobiol. (2010)

Bottom Line: PostC reduced infarct size to 34 ± 5%.CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP.These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

ABSTRACT
The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium.

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Systolic function: a Percent variation of developed LVP (dLVP) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. b Percent variation of first derivative of LVP during systole (dP/dtmax) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. * P < 0.05 with respect to I/R; # P < 0.05 with respect to CST-Post. Diastolic function: c Left ventricular end-diastolic pressure (LVEDP) (mmHg) during the 30-min ischemia and 120-min reperfusion. d Percent variation of first derivative of LVP during diastole (dP/dtmin) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. ** P < 0.01 with respect to I/R (for further explanation see text)
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Fig3: Systolic function: a Percent variation of developed LVP (dLVP) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. b Percent variation of first derivative of LVP during systole (dP/dtmax) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. * P < 0.05 with respect to I/R; # P < 0.05 with respect to CST-Post. Diastolic function: c Left ventricular end-diastolic pressure (LVEDP) (mmHg) during the 30-min ischemia and 120-min reperfusion. d Percent variation of first derivative of LVP during diastole (dP/dtmin) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. ** P < 0.01 with respect to I/R (for further explanation see text)

Mentions: In Fig. 3a and b, developed LVP (dLVP) and maximum rate of increase of LVP during systole (dP/dtmax) are reported as percent variation with respect to baseline level. The hearts of the I/R group present a marked limitation of dLVP recovery; in fact at the end of reperfusion dLVP was 34 ± 10% of baseline level (P < 0.001). PostC and CST-Post significantly improved the dLVP recovery during reperfusion (P < 0.05 with respect to I/R group, for both). Actually, the improvement observed after CST was significantly higher (P < 0.05) than that observed in PostC group. In particular, at the end of reperfusion the recovery was 52 ± 10% (P < 0.05) and 63 ± 23% (P < 0.05) of baseline levels for PostC and CST-Post, respectively (Fig. 3a). A similar trend was observed for dP/dtmax recovery during reperfusion in the three groups, though statistic differences were observed with respect to I/R group only, and not between PostC and CST-Post (Fig. 3b).


Catestatin improves post-ischemic left ventricular function and decreases ischemia/reperfusion injury in heart.

Penna C, Alloatti G, Gallo MP, Cerra MC, Levi R, Tullio F, Bassino E, Dolgetta S, Mahata SK, Tota B, Pagliaro P - Cell. Mol. Neurobiol. (2010)

Systolic function: a Percent variation of developed LVP (dLVP) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. b Percent variation of first derivative of LVP during systole (dP/dtmax) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. * P < 0.05 with respect to I/R; # P < 0.05 with respect to CST-Post. Diastolic function: c Left ventricular end-diastolic pressure (LVEDP) (mmHg) during the 30-min ischemia and 120-min reperfusion. d Percent variation of first derivative of LVP during diastole (dP/dtmin) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. ** P < 0.01 with respect to I/R (for further explanation see text)
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Fig3: Systolic function: a Percent variation of developed LVP (dLVP) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. b Percent variation of first derivative of LVP during systole (dP/dtmax) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion. Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. * P < 0.05 with respect to I/R; # P < 0.05 with respect to CST-Post. Diastolic function: c Left ventricular end-diastolic pressure (LVEDP) (mmHg) during the 30-min ischemia and 120-min reperfusion. d Percent variation of first derivative of LVP during diastole (dP/dtmin) with respect to baseline level for each group, during the 30-min ischemia and 120-min reperfusion Time 0 correspond to the beginning of reperfusion. PostC post-conditioning, CST catestatin. ** P < 0.01 with respect to I/R (for further explanation see text)
Mentions: In Fig. 3a and b, developed LVP (dLVP) and maximum rate of increase of LVP during systole (dP/dtmax) are reported as percent variation with respect to baseline level. The hearts of the I/R group present a marked limitation of dLVP recovery; in fact at the end of reperfusion dLVP was 34 ± 10% of baseline level (P < 0.001). PostC and CST-Post significantly improved the dLVP recovery during reperfusion (P < 0.05 with respect to I/R group, for both). Actually, the improvement observed after CST was significantly higher (P < 0.05) than that observed in PostC group. In particular, at the end of reperfusion the recovery was 52 ± 10% (P < 0.05) and 63 ± 23% (P < 0.05) of baseline levels for PostC and CST-Post, respectively (Fig. 3a). A similar trend was observed for dP/dtmax recovery during reperfusion in the three groups, though statistic differences were observed with respect to I/R group only, and not between PostC and CST-Post (Fig. 3b).

Bottom Line: PostC reduced infarct size to 34 ± 5%.CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP.These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

ABSTRACT
The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium.

Show MeSH
Related in: MedlinePlus