Skip main navigation
Cellular Biology
Session Title: Mitophagy/Autophagy and other Regulators of Ventricular Function

Abstract 11146: Genetic Deletion of Elovl6 in Cardiac Myocytes Suppresses Pressure Overload-Induced Cardiac Hypertrophy and Remodeling Through Activation of AMPK/KLF4 Signaling

Originally publishedCirculation. 2018;138:A11146

    Introduction: Intracellular long-chain fatty acid (LCFA) has a crucial role in a variety of cellular functions. Our recent study demonstrated that elongase of long chain fatty acids 6 (Elovl6), catalyzing the de novo synthesis of LCFA, contributes to the vascular smooth muscle cell proliferation and neointimal formation. Despite the heart utilizes FAs as major energy substrates, little is known about the role of Elovl6 in the heart.

    Hypothesis: Here we investigated its role of Elovl6 in cardiac remodeling using Elovl6-knockout mice during pressure overload.

    Methods and Results: We used a mouse model of cardiac hypertrophy following transverse aortic constriction (TAC) surgery. Myocardial hypertrophy and interstitial fibrosis examined by histological analysis was attenuated more in Elovl6-null (Elovl6-/-) mice at 1, 4 and 8 weeks after TAC than in wild-type (WT) mice. Echocardiography showed that the decrease in cardiac function induced by TAC was attenuated in Elovl6-/- mice at 4 and 8 weeks than in WT mice. The mRNA expressions of ANP, BNP and procollagen type I, III, well defined cardiac hypertrophic and fibrosis markers, was also less in the Elovl6-/- mice heart subjected to TAC. To clarify the effects of an Elovl6 deficiency on myocardial LCFA compositions, we examined the lipids extract from the mouse heart. An Elovl6 deficiency increased the proportion of palmitate levels, and decreased those of oleic acid. We previously reported that an Elovl6 deficiency suppressed neointimal formation via the activation of AMP-activated protein kinase (AMPK) and pluripotency gene Krüppel-like factor 4 (KLF4). Since the activation of AMPK or KLF4 has been known to suppress cardiac hypertrophy and myocardial fibrosis, we examined the effect of Elovl6-deficiency or palmitate in vivo or in vitro experiments. Indeed, the induction of AMPK and KLF4 expression was noted in the hearts of Elovl6-/- mice or in cultured neonatal rat ventricular myocytes exposed to either palmitate or Elovl6 siRNA.

    Conclusions: Our results provide a novel role of Elovl6-driven intracellular LCFA compositions in the regulation of hypertrophic responses during pressure overload through the activation of the AMPK/KLF4-axis, a newly identified signaling pathway controlling cardiac phenotype.


    Author Disclosures: H. Matsui: None. H. Sunaga: None. Y. Umbarawan: None. T. Iso: None. N. Koitabashi: None. T. Matsuzaka: None. H. Shimano: None. T. Yokoyama: None. M. Kurabayashi: None.


    eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

    Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.