Chronic urocortin 2 administration improves cardiac function and ameliorates cardiac remodeling after experimental myocardial infarction.

Abstract

The impact of chronic urocortin 2 (Ucn2) treatment after myocardial infarction (MI) has not previously been investigated. In this study, we examined the effects of 30-day Ucn2 administration (415 μg·kg·d SC per day) in mice post-MI. Compared with surgical sham + vehicle controls (n = 10), MI + vehicle animals (n = 10) after 30 days demonstrated decreased ejection fraction (75.6 ± 1.2 vs. 43.6% ± 0.8%, P < 0.001) and fractional shortening (38.20 ± 0.83 vs. 18.4% ± 0.54%, P < 0.001) in association with increased heart weight-to-body weight ratio (4.57 ± 0.25 vs. 5.29 ± 0.18, P < 0.01), left ventricular (LV) mass (91 ± 7 vs. 126 ± 8 mg, P < 0.01), LV internal diameters at both systole (1.91 ± 0.14 vs. 3.45 ± 0.09 mm, P < 0.001) and diastole (3.14 ± 0.15 vs. 4.25 ± 0.10 mm, P < 0.001), LV end systolic volumes (0.02 ± 0.01 vs. 0.11 ± 0.01 mL, P < 0.001), and ventricular collagen 1 and β-myosin heavy chain gene expression. Compared with MI + vehicle mice, MI + Ucn2 animals (n = 10) exhibited significantly reduced infarct size (4.00 ± 0.39 vs. 1.83 ± 0.44 mm, P < 0.01), heart weight-to-body weight ratio (4.75 ± 0.19, P = 0.06), LV mass (101 ± 6 mg, P < 0.01), LV internal diameters (systole 2.61 ± 0.09 mm, P < 0.001; diastole 3.78 ± 0.09 mm, P < 0.001), and end systolic volumes (0.14 ± 0.02 mL, P < 0.01) in conjunction with improved ejection fraction (65.2% ± 0.9%, P < 0.001) and fractional shortening (18.4 ± 0.5 vs. 30.5% ± 0.5%, P < 0.001). Ucn2 treatment also decreased collagen 1 and β-myosin heavy chain expression. In conclusion, chronic Ucn2 treatment significantly improves cardiovascular function and attenuates cardiac injury and remodeling in experimental MI.

• Authors: Leigh J Ellmers, Nicola J A Scott, Vicky A Cameron, A Mark Richards, Miriam T Rademaker
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 65 Issue 3 Pg. 269-75 (Mar 2015) ISSN: 1533-4023 [Electronic] United States
• PMID: 25658462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Collagen Type I
• Myh7 protein, mouse
• RNA, Messenger
• Urocortins
• Myosin Heavy Chains

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Collagen Type I (genetics, metabolism)
• Disease Models, Animal
• Fibrosis
• Gene Expression Regulation
• Hemodynamics (drug effects)
• Hypertrophy, Left Ventricular (genetics, metabolism, pathology, physiopathology, prevention & control)
• Male
• Mice, Inbred C57BL
• Myocardial Contraction (drug effects)
• Myocardial Infarction (drug therapy, genetics, metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Myosin Heavy Chains (genetics, metabolism)
• RNA, Messenger (metabolism)
• Recovery of Function
• Stroke Volume (drug effects)
• Time Factors
• Urocortins (pharmacology)
• Ventricular Dysfunction, Left (genetics, metabolism, pathology, physiopathology, prevention & control)
• Ventricular Function, Left (drug effects)
• Ventricular Remodeling (drug effects)