Abstract
Consequences of Enhanced CGRP Receptor Signaling on Cardiac Function and Mortality Post‐Myocardial Infarction
The FASEB journal, Vol.24(S1), pp.1037.4-1037.4
04/2010
DOI: 10.1096/fasebj.24.1_supplement.1037.4
Abstract
Calcitonin gene‐related peptide (CGRP) is a powerful vasodilator released from cardiac sensory nerves post‐myocardial infarction (MI). We have shown that ubiquitous overexpression of the CGRP receptor subunit Receptor Activity‐Modifying Protein 1 (RAMP1) enhances CGRP receptor signaling and attenuates angiotensin‐induced hypertension (J Neurosci 2007, Hypertension 2007). We hypothesized that transgenic expression of RAMP1 will improve cardiac function and prolong survival post‐MI. RAMP1 mice (n=28) and littermate controls (n=22) underwent left coronary ligation or sham surgery at 12–15 wks of age. Control mice with MI (15–19 wks post‐surg) exhibited left ventricular (LV) dysfunction (echocardiogram), cardiac hypertrophy, decreased wheel‐running activity (revs/hr) and 50% mortality (Table, *P<.05). RAMP1 mice were not protected post‐MI; LV ejection fraction (LVEF) was reduced, heart weight/body weight (HW/BW, mg/g) was increased, MI size was increased (64±4 vs. 44±3 %), and mortality was increased (67% vs. 50%)(†P<.05 vs. controls). Interestingly, the MI‐induced decrease in wheel‐running was abrogated in RAMP1 mice (Table).
LVEF
HW/BW
Activity
Sham (S) n=10
.76±.03
4.8±0.2
296±79
MI n=7
.49±.06*
6.1±0.3*
127±45*
RAMP1‐S n=8
.70±.03
5.8±0.2
245±121
RAMP1‐MI n=6
.27±.03*†
8.3±0.9*†
392±137†
We conclude: 1) RAMP1 mice are not protected post‐MI, but instead exhibit marked LV dysfunction and increased mortality; and 2) Despite LV dysfunction, wheel‐running activity is preserved post‐MI in RAMP1 mice. Ubiquitous RAMP1 overexpression may lead to deleterious actions of CGRP that compromise cardiac function. Thus, tissue‐selective targeting of RAMP1 may be critical for therapeutic benefit. (AHA‐0855944G, RR017369, HL14388, VA)
Details
- Title: Subtitle
- Consequences of Enhanced CGRP Receptor Signaling on Cardiac Function and Mortality Post‐Myocardial Infarction
- Creators
- Veronica A Peotta - University of IowaRobert M Weiss - University of IowaKathy A Zimmerman - United States Department of Veterans AffairsYongjun Lu - University of IowaAndrew F Russo - University of IowaFrancois M Abboud - University of IowaMark W Chapleau - United States Department of Veterans Affairs
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.24(S1), pp.1037.4-1037.4
- DOI
- 10.1096/fasebj.24.1_supplement.1037.4
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- Federation of American Societies for Experimental Biology
- Number of pages
- 1
- Language
- English
- Date published
- 04/2010
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984302999502771
Metrics
11 Record Views