Chronic Akt1 deficiency attenuates adverse remodeling and enhances angiogenesis after myocardial infarction.

نویسندگان

  • Katrien Vandoorne
  • Moriel H Vandsburger
  • Tal Raz
  • Moran Shalev
  • Karen Weisinger
  • Inbal Biton
  • Vlad Brumfeld
  • Calanit Raanan
  • Nava Nevo
  • Raya Eilam
  • Brian A Hemmings
  • Eldad Tzahor
  • Alon Harmelin
  • Lior Gepstein
  • Michal Neeman
چکیده

BACKGROUND Akt1 is a key signaling molecule in multiple cell types, including endothelial cells. Accordingly, Akt1 was proposed as a therapeutic target for ischemic injury in the context of myocardial infarction (MI). The aim of this study was to use multimodal in vivo imaging to investigate the impact of systemic Akt1 deficiency on cardiac function and angiogenesis before and after MI. METHODS AND RESULTS In vivo cardiac MRI was performed before and at days 1, 8, 15, and 29 to 30 after MI induction for wild-type, heterozygous, and Akt1-deficient mice. Noninfarcted hearts were imaged using ex vivo stereomicroscopy and microcomputed tomography. Histological examination was performed for noninfarcted hearts and for hearts at days 8 and 29 to 30 after MI. MRI revealed mildly decreased baseline cardiac function in Akt1 null mice, whereas ex vivo stereomicroscopy and microcomputed tomography revealed substantially reduced coronary macrovasculature. After MI, Akt1(-/-) mice demonstrated significantly attenuated ventricular remodeling and a smaller decrease in ejection fraction. At 8 days after MI, a larger functional capillary network at the remote and border zone, accompanied by reduced scar extension, preserved cardiac function, and enhanced border zone wall thickening, was observed in Akt1(-/-) mice when compared with littermate controls. CONCLUSIONS Using multimodal imaging to probe the role of Akt1 in cardiac function and remodeling after MI, this study revealed reduced adverse remodeling in Akt1-deficient mice after MI. Augmented myocardial angiogenesis coupled with a more functional myocardial capillary network may facilitate revascularization and therefore be responsible for preservation of infarcted myocardium.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Chronic Akt1 Deficiency Attenuates Adverse Remodeling and Enhances Angiogenesis After Myocardial Infarction Vandoorne et al: Cardiac Protective Effects of Akt1 Deficiency

متن کامل

Intermedin1–53 enhances angiogenesis and attenuates adverse remodeling following myocardial infarction by activating AMP-activated protein kinase

Adverse ventricular remodeling is a maladaptive response to acute loss of myocardium and an important risk factor for heart failure following myocardial infarction (MI). Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene‑related peptide family, which may possess potent cardioprotective properties. The aim of the present study was to determine whether IMD1‑53, a mature bioactiv...

متن کامل

Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction.

BACKGROUND It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling following myocardial infarction. In contrast, little is known about the effects of increasing skeletal muscle mass, typically achieved through resistance training, on this process. Here, we utilized transgenic (TG) mice that can induce the growth of functional skeletal muscle by switchin...

متن کامل

Akt1-Mediated Skeletal Muscle Growth Attenuates Cardiac Dysfunction and Remodeling after Experimental Myocardial Infarction Araki et al: Muscle Growth Attenuates Cardiac Remodeling

Background It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling post myocardial infarction (MI). In contrast, little is known about the effects of increasing skeletal muscle mass, typically achieved through resistance training, on this process. Here, we utilized transgenic (TG) mice, that can induce the growth of functional skeletal muscle by switchi...

متن کامل

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction.

OBJECTIVE Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Circulation. Cardiovascular imaging

دوره 6 6  شماره 

صفحات  -

تاریخ انتشار 2013