Axl expression is increased in early stages of left ventricular remodeling in an animal model with pressure-overload.

BACKGROUND

AXL is a receptor tyrosine kinase that has been related to kidney and vascular disorders. Heart failure patients with reduced ejection fraction have higher AXL in serum than controls. No information about Axl expression with HF progression is available.

METHODS

Thoracic transverse aortic constriction (TAC) was successfully performed on male Wistar rats (n = 25) with different constriction levels. Controls underwent sham surgery (n = 12). Echocardiography measurements were performed 4-8 weeks after surgery. Collagen deposition was measured with picrosirius red staining. Axl mRNA levels in left ventricle (LV), left kidney (LK) and ascending aorta (aAo) and the LV expression of cardiac remodeling and fibrogenic factors were quantified with real-time PCR. AXL LV protein levels were quantified with western blot and localization was analyzed by immunohistochemistry. Soluble AXL levels in plasma were assayed with ELISA.

RESULTS

Successful TAC rats were classified into LV hypertrophy (LVH) or heart failure (HF), modeling the progressive cardiac changes after pressure overload. Collagen deposition was increased only in the HF group. LV Axl mRNA levels were higher in LVH and HF than in Sham rats, and correlated with LVHi, and hypertrophic and fibrogenic mediators. However, no association was found with LV systolic function. AXL was expressed in LV myocytes and other cell types. Concentration of circulating sAXL in plasma was increased in the LVH group compared to Sham and HF rats. Axl mRNA levels were similar in all groups in the LK and aAo.

CONCLUSIONS

Axl expression pattern suggests a role in the early progression of LV remodeling in HF but not in the later systolic dysfunction. The higher levels of circulating AXL found in HF patients most probably shed from the heart.

Déclaration de conflit d'intérêts

Pablo García de Frutos and Montserrat Batlle are the inventors of the patent “Use of soluble form of AXL in the diagnosis and/or prognosis of heart failure syndrome” with the international number of publication WO 2013/120830 A1, published on 22/08/2013. This patent is not currently licensed to any industry and there are no products in development or modified products and we are not employed or receive consultancies from industries. This patent does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Also, the authors want to share that Pablo Garcia de Frutos is currently a PLOS ONE editor.