Inhibition of MAPK signaling by eNOS gene transfer improves ventricular remodeling after myocardial infarction through reduction of inflammation

Abstract

Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) may play an important role in attenuating cardiac remodeling and apoptosis after myocardial infarction. However, the anti-inflammation effects of eNOS in infarcted myocardium and the role of MAPK signaling in eNOS/NO mediated cardiac remodeling have not yet been elucidated. Adenovirus carrying Human eNOS gene was delivered locally into heart 4 days prior to induction of myocardial infarction (MI) by left anterior descending coronary artery ligation. Monocyte/macrophage infiltration was detected by ED-1 immunohistochemistry. Western blot was employed to examine the activation of MAPK. eNOS gene transfer significantly reduced myocardial infarct size and improved cardiac contractility as well as left ventricle (LV) diastolic function at 7 days after MI. In addition, eNOS gene transfer decreased monocyte/macrophage infiltration in the infarct region of the heart. Phosphorylation of MAPK after MI were also dramatically reduced by eNOS gene transfer. All the protective effects of eNOS were blocked by N(ω)-nitro-L-arginine methyl ester (L-NAME) administration, indicating a NO-mediated event. These results demonstrate that the eNOS/NO system provides cardiac protection after MI injury through inhibition of inflammation and suppression of MAPK signaling.

Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction

“…To elucidate how MIF regulates inflammatory signalling following MI, we performed immunoblotting for p38 and JNK MAPK, both are important in inflammatory signalling post MI [29–31]. There was no difference between sham-operated WT and MIFKO groups in levels of phosphorylated p38 or JNK (Figure 4A and 4B).…”

A Network Study of Chinese Medicine Xuesaitong Injection to Elucidate a Complex Mode of Action with Multicompound, Multitarget, and Multipathway

“…In addition, many inflammatory response related pathways were also enriched, including complement and coagulation cascades, Fc epsilon RI signaling pathway, hematopoietic cell lineage, leukocyte transendothelial migration, NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway, and Toll-like receptor signaling pathway. It was suggested that XST modulates inflammatory responses in treating ischemia, which has been found to prevent damages of the inflammatory factors to cardiac cells [34–37]. The influencing in complement and coagulation cascades pathway indicated that XST and its constituent compound notoginsenoside R1 are functional in modulating the coagulation process in MI, which is one of the most common clinical risk factors [32–35].…”

Potential new role of the GHSR-1a-mediated signaling pathway in cardiac remodeling after myocardial infarction (Review)

“…One of the most important factors for improving the prognosis after MI is the attenuation of adverse myocardial remodeling and pathological left ventricular hypertrophy. It is well known that several key signaling pathways are involved in the remodeling process, such as the PI3K/Akt (34) and AMPK (35) signaling pathways. Given such complexity in GHSR-1a signaling, we hypothesize that GHSR-1a may play an important regulatory role in cardiac protection.…”