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Published on: January 18, 2019
The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo
Euan A Ashley1, Jennifer Powers, Mary Chen
1Donald W. Reynolds Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USA. euan@stanford.edu
Insights
Apelin peptide administration improved cardiac function by reducing left ventricular preload and afterload, enhancing contractile reserve without causing hypertrophy. This suggests apelin as a promising therapeutic target for heart failure.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Pharmacology
Background:
- The endogenous peptide apelin plays a role in cardiovascular regulation, but its specific function in cardiac performance is not fully understood.
- Apelin levels are altered in cardiovascular diseases, highlighting its potential involvement in disease pathophysiology.
Purpose of the Study:
- To investigate the functional impact of apelin on cardiac function in vivo.
- To determine the effects of acute and chronic apelin administration on cardiac hemodynamics and structure.
- To examine the expression and localization of apelin and its receptor (APJ) in the developing and adult heart.
Main Methods:
- Utilized ECG and MRI for in vivo cardiac assessment.
- Employed conductance catheter pressure-volume loops for detailed hemodynamic measurements.
- Conducted echocardiography to evaluate cardiac output and contractility.
- Performed histology and immunohistochemistry to assess cardiac hypertrophy and apelin/APJ distribution.
Main Results:
- Acute apelin injection decreased left ventricular end-diastolic area and increased heart rate, ventricular elastance, and preload recruitable stroke work.
- Chronic apelin infusion significantly enhanced the velocity of circumferential shortening and cardiac output.
- No significant differences in heart weight or cellular hypertrophy were observed between apelin and saline groups.
- APJ was localized in adult myocardial cells, and both apelin and APJ were expressed in embryonic hearts.
Conclusions:
- Apelin administration favorably modulated cardiac hemodynamics by reducing preload and afterload.
- Apelin enhanced contractile reserve without inducing cardiac hypertrophy.
- These findings support apelin as a potential therapeutic agent for managing heart failure.
Objective:
The endogenous peptide apelin is differentially regulated in cardiovascular disease but the nature of its role in cardiac function remains unclear.
Methods:
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.
Results:
Intraperitoneal injection of apelin (300 microg/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.
Conclusions:
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.
