Apelin antagonizes myocardial impairment in sepsis.
BACKGROUND
Apelin is a cardiovascular peptide with multiple functions regulating homeostasis of the circulatory system and is the endogenous ligand of angiotensin II receptor like-1 (AGTRL1). Apelin has anti-inflammatory and inhibitory effects on release of inflammatory mediators. We aimed to analyze whether apelin antagonizes myocardial impairment in sepsis by attenuating inflammatory responses.


RESULTS
Male rats underwent sepsis by cecal ligation and puncture (CLP) after receiving low- or high-dose apelin for 3 days. Twenty hours later, rats with sepsis showed severe disturbance of hemodynamic features. Reverse transcription-polymerase chain reaction revealed decreased mRNA levels of apelin and AGTRL1 in myocardia of rats with sepsis. Enzyme immune assay detected a lower level of apelin in plasma and myocardia. Western blot analysis revealed decreased level of myocardial AGTRL1 protein. Low- and high-dose apelin administration ameliorated disorders of cardiac function: increased mean arterial blood pressure, attenuated heart rate, elevated +LVdp/dt(max) and LVdp/dt(max), and lowered left ventricular end-diastolic pressure. Rats treated with low- or high-dose apelin showed lower content of plasma monocyte chemoattractant protein 1 and interleukin 8. In cultured rat peritoneal macrophages, apelin directly inhibited the production of monocyte chemoattractant protein 1 and interleukin-8 induced by lipopolysaccharide.


CONCLUSIONS
These results suggest that apelin antagonizes cardiac impairment in sepsis by attenuating inflammatory responses and might be a promising therapeutic target for severe sepsis and septic shock.
Pan
Chun-Shui
CS
Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Beijing, China.
Teng
Xu
X
Zhang
Jing
J
Cai
Yan
Y
Zhao
Jing
J
Wu
Wei
W
Wang
Xian
X
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D000818:Animals; D000073861:Apelin; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000502:physiology* / Q000627:therapeutic use; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology
D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins