Midkine exacerbates pressure overload-induced cardiac remodeling

Abstract

Midkine is a multifunctional growth factor, and its serum levels are increased with the functional severity of heart failure. This study aimed to examine the role of midkine in heart failure pathogenesis. Midkine expression levels were increased in the kidney and lung after transverse aortic constriction (TAC) surgery, but not sufficiently increased in the heart. After TAC, phosphorylation of extracellular signal-regulated kinase1/2 and AKT, and the expression levels of foetal genes in the heart were considerably increased in transgenic mice with cardiac-specific overexpression of midkine (MK-Tg) compared with wild-type (WT) mice. MK-Tg mice showed more severe cardiac hypertrophy and dysfunction, and showed lower survival rate after TAC than WT mice. We conclude that midkine plays a critical role in cardiac hypertrophy and remodelling.

Midkine Deteriorates Cardiac Remodeling via Epidermal Growth Factor Receptor Signaling in Chronic Kidney Disease

“…15 Moreover, we recently reported that cardiac-specific overexpression of midkine exacerbates cardiac remodeling after pressure overload. 28 In this study, we confirmed that midkine induced ERK1/2 and AKT phosphorylation and hypertrophy in cardiomyocytes. These data suggest that circulating midkine might directly induce strong and broad effects in the heart through ERK and AKT activation.…”

Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits

“…We also demonstrated that exogenous MK application predominantly increases its anti-apoptotic effect and prevents cardiac remodeling in cHF rabbits created by ventricular tachycardia pacing. On the other hand, netsu et al [33] have shown that MK overexpression enhances ventricular dysfunction in mice subjected to pressure overload via activation of both erK 1/2 and akt signaling, increasing hypertrophic response and fibrosis. MK is a double-edged sword: it promotes detrimental inflammation but also inhibits cell apoptosis.…”

High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis

“…[21,22] The adequacy of anesthesia was monitored at all times by assessing of skeletal muscle tone, respiration rate and rhythm, and response to tail pinch.…”

“…Real-time RT-PCR amplification was performed as previously described, [21,22] and gene expression levels were normalized relative to levels of transcripts that encode glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Primers were designed using sequences deposited in GenBank (HSPB1, NM_031970; GAPDH, NM_017008).…”