TY - JOUR
T1 - The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo
AU - Ashley, Euan A.
AU - Powers, Jennifer
AU - Chen, Mary
AU - Kundu, Ramendra
AU - Finsterbach, Tom
AU - Caffarelli, Anthony
AU - Deng, Alicia
AU - Eichhorn, Jens
AU - Mahajan, Raina
AU - Agrawal, Rani
AU - Greve, Joan
AU - Robbins, Robert
AU - Patterson, Andrew J.
AU - Bernstein, Daniel
AU - Quertermous, Thomas
N1 - Funding Information:
This work was supported by the Donald W. Reynolds Cardiovascular Clinical Research Center at Stanford University.
PY - 2005/1/1
Y1 - 2005/1/1
N2 - The endogenous peptide apelin is differentially regulated in cardiovascular disease but the nature of its role in cardiac function remains unclear. We investigated the functional relevance of this peptide using ECG and respiration gated magnetic resonance imaging, conductance catheter pressure-volume hemodynamic measurements, and echocardiography in vivo. In addition, we carried out histology and immunohistochemistry to assess cardiac hypertrophy and to localize apelin and APJ in the adult and embryonic mouse heart. Intraperitoneal injection of apelin (300 μg/kg) resulted in a decrease in left ventricular end diastolic area (pre: 0.122±0.007; post: 0.104±0.005 cm 2, p=0.006) and an increase in heart rate (pre: 537±20; post: 559±19 beats per minute, p=0.03). Hemodynamic measurements revealed a marked increase in ventricular elastance (pre: 3.7±0.9; post: 6.5±1.4 mm Hg/RVU, p=0.018) and preload recruitable stroke work (pre: 27.4±8.0; post: 51.8±3.1, p=0.059) with little change in diastolic parameters following acute infusion of apelin. Chronic infusion (2 mg/kg/day) resulted in significant increases in the velocity of circumferential shortening (baseline: 5.36±0.401; 14 days: 6.85±0.358 circ/s, p=0.049) and cardiac output (baseline: 0.142±0.019; 14 days: 0.25±0.019 l/min, p=0.001) as determined by 15 MHz echocardiography. Post-mortem corrected heart weights were not different between apelin and saline groups (p=0.5) and histology revealed no evidence of cellular hypertrophy in the apelin group (nuclei per unit area, p=0.9). Immunohistochemistry studies revealed APJ staining of myocardial cells in all regions of the adult mouse heart. Antibody staining, as well as quantitative real time polymerase chain reaction identified expression of both APJ and apelin in embryonic myocardium as early as embryonic day 13.5. Apelin reduces left ventricular preload and afterload and increases contractile reserve without evidence of hypertrophy. These results associate apelin with a positive hemodynamic profile and suggest it as an attractive target for pharmacotherapy in the setting of heart failure.
AB - The endogenous peptide apelin is differentially regulated in cardiovascular disease but the nature of its role in cardiac function remains unclear. We investigated the functional relevance of this peptide using ECG and respiration gated magnetic resonance imaging, conductance catheter pressure-volume hemodynamic measurements, and echocardiography in vivo. In addition, we carried out histology and immunohistochemistry to assess cardiac hypertrophy and to localize apelin and APJ in the adult and embryonic mouse heart. Intraperitoneal injection of apelin (300 μg/kg) resulted in a decrease in left ventricular end diastolic area (pre: 0.122±0.007; post: 0.104±0.005 cm 2, p=0.006) and an increase in heart rate (pre: 537±20; post: 559±19 beats per minute, p=0.03). Hemodynamic measurements revealed a marked increase in ventricular elastance (pre: 3.7±0.9; post: 6.5±1.4 mm Hg/RVU, p=0.018) and preload recruitable stroke work (pre: 27.4±8.0; post: 51.8±3.1, p=0.059) with little change in diastolic parameters following acute infusion of apelin. Chronic infusion (2 mg/kg/day) resulted in significant increases in the velocity of circumferential shortening (baseline: 5.36±0.401; 14 days: 6.85±0.358 circ/s, p=0.049) and cardiac output (baseline: 0.142±0.019; 14 days: 0.25±0.019 l/min, p=0.001) as determined by 15 MHz echocardiography. Post-mortem corrected heart weights were not different between apelin and saline groups (p=0.5) and histology revealed no evidence of cellular hypertrophy in the apelin group (nuclei per unit area, p=0.9). Immunohistochemistry studies revealed APJ staining of myocardial cells in all regions of the adult mouse heart. Antibody staining, as well as quantitative real time polymerase chain reaction identified expression of both APJ and apelin in embryonic myocardium as early as embryonic day 13.5. Apelin reduces left ventricular preload and afterload and increases contractile reserve without evidence of hypertrophy. These results associate apelin with a positive hemodynamic profile and suggest it as an attractive target for pharmacotherapy in the setting of heart failure.
KW - APJ
KW - Angiotensin
KW - Apelin
KW - Heart failure
KW - Pressure-volume hemodynamics
UR - http://www.scopus.com/inward/record.url?scp=19944373052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19944373052&partnerID=8YFLogxK
U2 - 10.1016/j.cardiores.2004.08.018
DO - 10.1016/j.cardiores.2004.08.018
M3 - Article
C2 - 15621035
AN - SCOPUS:19944373052
SN - 0008-6363
VL - 65
SP - 73
EP - 82
JO - Cardiovascular research
JF - Cardiovascular research
IS - 1
ER -