Serum levels of Growth Arrest-Specific 6 protein and soluble AXL in patients with ST-segment elevation myocardial infarction

Caldentey, Guillem; Frutos, Pablo García de; Cristóbal, Helena; Garabito, Manel; Berruezo, Antonio; Bosch, Xavier; Antonio, Rodolfo San; Flores‐Umanzor, Eduardo; Perea, Rosario J.; Caralt, Teresa M. de; Rodríguez, J; Ortiz-Pérez, Josè T.

doi:10.1177/2048872617740833

Cited by 21 publications

(28 citation statements)

References 41 publications

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“…In cardiac transplant recipients, sAXL values were higher in those presenting with adverse CV events, an association that remained significant after multivariate adjustment [18]. After an ST-elevation AMI, higher sAXL levels flag those patients who will develop HF and an adverse LV remodeling during follow-up [19]. We have reported that sAXL is a good prognostic marker of the HF major events all-cause mortality, transplantation and HF hospitalizations at 1 year [20] and at 3.6 years follow-up [29].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

“…Gas6 (-/-) mice lacking the Axl-ligand Gas6 are protected from pressure-overload left ventricle (LV) remodeling and fibrosis, while LV remodeling was remarkably increased in mice with Gas6 cardiac overexpression [17]. In humans, sAXL evolves as an attractive biomarker for HF and other cardiac conditions [18,19].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…In patients with heart failure Axl levels are amplified both in terms of the cardiac tissue and circulating soluble Axl (sAxl) 35 . Furthermore, Gas6 and sAxl levels are found to increase in patients following ST-segment elevation MI 96 . In both studies, the levels of Axl were predictive of adverse pathology, such as the extent of left ventricular remodelling and of further cardiovascular events.…”

Section: Axl In Cvdmentioning

confidence: 97%

“…Although Tyro3 could potentially have a protective effect on the myocardium, as it suppresses Th2 responses which drive cardiac fibrosis, 136 , 140–142 a direct causal link has not been shown to date. Gas6-Axl driven activation of the ERK signalling cascade in cardiomyocytes is implemented in the pathological remodelling which occurs in heart failure patients 35 , 96 , 97 . Numerous studies have highlighted Axl to also have a pathological role in vascular remodelling through increasing VSMC proliferation, migration, and immune activation, while also inhibiting VSMC apoptosis 64 , 65 , 69 , 79 …”

Section: Conclusion and Future Questionsmentioning

confidence: 99%

TAM receptors in cardiovascular disease

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Lemke

et al. 2019

Cardiovascular Research

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The TAM receptors are a distinct family of three receptor tyrosine kinases, namely Tyro3, Axl, and MerTK. Since their discovery in the early 1990s, they have been studied for their ability to influence numerous diseases, including cancer, chronic inflammatory and autoimmune disorders, and cardiovascular diseases. The TAM receptors demonstrate an ability to influence multiple aspects of cardiovascular pathology via their diverse effects on cells of both the vasculature and the immune system. In this review, we will explore the various functions of the TAM receptors and how they influence cardiovascular disease through regulation of vascular remodelling, efferocytosis and inflammation. Based on this information, we will suggest areas in which further research is required and identify potential targets for therapeutic intervention.

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“…AXL is involved in the angiogenesis regulation. It was found that patients with heart failure and severe left ventricular remodeling processes have a higher level of sAXL, which indicates the potential role of the GAS6-AXL system in the pathophysiology of these processes (Caldentey et al, 2019). Increased AXL expression in arteries was revealed in patients after coronary artery bypass grafting.…”

Section: Discussionmentioning

confidence: 98%

The Effect of Five-Day Dry Immersion on the Nervous and Metabolic Mechanisms of the Circulatory System

et al. 2020

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The purpose of the study was to investigate the regulatory and metabolic changes in the circulatory system when simulating microgravity conditions in a five-day dry immersion. These changes reflect the adaptation processes characteristic for the initial stages of a space flight or a short-duration space flight. Studies were conducted with 13 healthy male volunteers aged 21 to 29 years. The assessment of regulatory and metabolic processes in the circulatory system was based on the heart rate variability (HRV) and urine proteomic profile analysis. It was found that the restructuring of hemodynamics during 5 days hypogravity begins with the inclusion of the nervous circuit of regulation, and for manifestations at the body fluids protein composition level and activation of the metabolic regulation, these periods are apparently insufficient. Perhaps this is due to the fact that the metabolic regulation, being evolutionarily ancient and genetically determined, is more stable and requires more time for its pronounced activation when stimulated by extreme life conditions.

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Serum levels of Growth Arrest-Specific 6 protein and soluble AXL in patients with ST-segment elevation myocardial infarction

Cited by 21 publications

References 41 publications

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

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

TAM receptors in cardiovascular disease

The Effect of Five-Day Dry Immersion on the Nervous and Metabolic Mechanisms of the Circulatory System

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