Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure.

نویسندگان

  • Federica Del Monte
  • Karyn Butler
  • Wolfgang Boecker
  • Judith K Gwathmey
  • Roger J Hajjar
چکیده

Aortic banding in the rat has become a popular method to induce left ventricular (LV) hypertrophy and heart failure. However, because of often extensive intrathoracic adhesions and inflammatory cell infiltrates resulting from the traditional surgical approach, an uncomplicated second thoracic incision for genetic manipulation is impeded. In this study, we describe a novel surgical technique of aortic banding which avoids opening the sternum and thereby avoids adhesions and surgery-related inflammation. Placing a clip on the ascending aorta using a suprasternal approach in Sprague-Dawley rats created proximal aortic constriction. The present study was initiated to determine whether a replication-deficient adenovirus would enable efficient gene transfer to adult cardiac myocytes undergoing hypertrophy and transitioning to heart failure. Echocardiography performed at week 24 revealed significant concentric hypertrophy and increased fractional shortening followed by LV dilatation with decreased fractional shortening after 27 wk of banding. An adenoviral solution encoding for the reporter green fluorescent protein gene (GFP) was delivered to the heart. Fluorescent microscopy revealed global gene expression throughout hypertrophied and failing hearts. Our studies demonstrate that a novel suprasternal approach can be applied to create an LV hypertrophy model followed by heart failure which also allows investigators to perform genetic manipulations in vivo through gene transfer without the complication of adhesions and surgical trauma-induced inflammation. Furthermore, our approach to delivery of transgenes results in homogenous gene expression in both hypertrophied and failing hearts.

برای دانلود رایگان 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

1, 25 Dihydroxyvitamin D3 Protects the Heart Against Pressure Overload-induced Hypertrophy without Affecting SIRT1 mRNA Level

Background and Aims: There has been scant information concerning antihypertrophic effects of vitamin D specifically on its cellular and molecular mechanisms. Sirtuin 1 (SIRT1) is regarded as a key deacetylase enzyme in cardiomyocytes which applies potential cardioprotective effects by functional regulation of different proteins. This study aimed to evaluate the effects of 1, 25-dihydroxyvitamin...

متن کامل

Role of oxidative stress in the aortic constriction-induced ventricular hypertrophy in rat

Introduction:Severe abdominal aortic constriction above the renal arteries induces arterial hypertension above the stenotic site that is the cause of cardiac hypertrophy. Previous studies have shown that high blood pressure induces myocardial oxidative stress with conflicting results. In the present study, we assessed the effects of acute hypertension on the myocardial oxidative stress an...

متن کامل

SOCS1 gene transfer accelerates the transition to heart failure through the inhibition of the gp130/JAK/STAT pathway.

AIMS The suppressors of cytokine signalling (SOCS) are identified inhibitors of cytokine and growth factor signalling that act via the Janus kinase (JAK) signal transducers and activators of transcription (STAT) pathways. Aberrant JAK/STAT signalling promotes progression from hypertrophy to heart failure. Little information is available concerning the role of SOCS in the transition from hypertr...

متن کامل

The effect of carvacrol on transcription levels of Bcl-2 family proteins in hypertrophied heart of rats

Introduction: Cardiomyocytes apoptosis contributes to the development of left ventricular hypertrophy. The Bcl-2 family members are important regulators of mitochondrial pathway of apoptosis. Monoterpenoid phenol –carvacrol– possesses strong antioxidant properties. The present study aimed to evaluate the effect of carvacrol on transcription level of pro-apoptotic (Bad and Bax) and...

متن کامل

Decompensation of Pressure-Overload Hypertrophy in Gaq-Overexpressing Mice

Background—Receptor-mediated activation of myocardial Gq signaling is postulated as a biochemical mechanism transducing pressure-overload hypertrophy. The specific effects of Gq activation on the functional and morphological adaptations to pressure overload are not known. Methods and Results—To determine the effects of intrinsic myocyte Gaq signaling on the left ventricular hypertrophic respons...

متن کامل

ذخیره در منابع من


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

عنوان ژورنال:
  • Physiological genomics

دوره 9 1  شماره 

صفحات  -

تاریخ انتشار 2002