Bone marrow-derived AXL tyrosine kinase promotes mitogenic crosstalk and cardiac allograft vasculopathy

Glinton, Kristofor; DeBerge, Matthew; Fisher, Emily; Schroth, Samantha; Sinha, Arjun; Wang, Jiao Jing; Wasserstrom, J. Andrew; Ansari, M. Javeed; Zhang, Zheng Jenny; Feinstein, Matthew J.; Leventhal, Joseph R.; Forbess, Joseph M.; Lomasney, Jon W.; Luo, Xunrong; Thorp, Edward B.

doi:10.1016/j.healun.2021.03.006

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…Aside from advances in imaging, there has been a concurrent search for biomarkers associated with CAV for early detection and as potential treatment targets. These include osteopontin, a pro-inflammatory cytokine that correlates with severe CAV [39]; endothelin-1, a vasoconstrictor peptide associated with accelerated CAV development [40]; and various microRNAs [41][42][43], among others [44][45][46][47][48]. These markers still require prospective validation to assess their utility in CAV detection, as well as continued evaluation as possible treatment targets.…”

Section: Cardiac Allograft Vasculopathy Detectionmentioning

confidence: 99%

Noninvasive methods to reduce cardiac complications postheart transplant

Zhou

Wolfson

Vaidya

2021

Current Opinion in Organ Transplantation

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Purpose of reviewLong-term success of heart transplantation is limited by allograft rejection and cardiac allograft vasculopathy (CAV). Classic management has relied on frequent invasive testing to screen for early features of rejection and CAV to allow for early treatment. In this review, we discuss new developments in the screening and prevention of allograft rejection and CAV. Recent findingsNewer noninvasive screening techniques show excellent sensitivity and specificity for the detection of clinically significant rejection. New biomarkers and treatment targets continue to be identified and await further studies regarding their utility in preventing allograft vasculopathy. SummaryNoninvasive imaging and biomarker testing continue to show promise as alternatives to invasive testing for allograft rejection. Continued validation of their effectiveness may lead to new surveillance protocols with reduced frequency of invasive testing. Furthermore, these noninvasive methods will allow for more personalized strategies to reduce the complications of long-term immunosuppression whereas continuing the decline in the overall rate of allograft rejection.

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Section: Cardiac Allograft Vasculopathy Detectionmentioning

confidence: 99%

Noninvasive methods to reduce cardiac complications postheart transplant

Zhou

Wolfson

Vaidya

2021

Current Opinion in Organ Transplantation

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“…AXL-deficient recipient mice displayed fewer immune cells and reduced neointima formation in grafted vessels. This function was linked to AXL expression in myeloid cells [ 30 ]. Interestingly, gas6 knockout animals also show an improved allograft heart survival, suggesting that GAS6 interaction with AXL is mediating this effect [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Soluble AXL in Serum from Heart Failure Patients with Preserved and Reduced Left Ventricular Ejection Fraction

Cristóbal

Enjuanes

Batlle

et al. 2023

JPM

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Heart failure (HF) is classified according to the degree of reduction in left ventricular ejection fraction (EF) in HF with reduced, mildly reduced, and preserved EF. Biomarkers could behave differently depending on EF type. Here, we analyze the soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF. Two groups of HF patients with reduced (HFrEF; n = 134) and preserved ejection fraction (HFpEF; n = 134) were included in this prospective observational study, with measurements of candidate biomarkers and functional, clinical, and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events: cardiovascular mortality and all-cause mortality. sAXL circulating values predicted outcome in HF: for a 1.0 ng/mL increase in serum sAXL, the mortality hazard ratio (HR) was 1.019 for HFrEF (95% CI 1.000 to 1.038) and 1.032 for HFpEF (95% CI 1.013 to 1.052). In a multivariable Cox regression analysis, sAXL and NT-proBNP were independent markers for all-cause and cardiovascular mortality in HFpEF. In contrast, only NT-proBNP remained significant in the HFrEF group. When analyzing the event-free survival at a mean follow-up of 3.6 years, HFrEF and HFpEF patients in the higher quartile of sAXL had a reduced survival time. Interestingly, sAXL is a reliable predictor for all-cause and cardiovascular mortality only in the HFpEF cohort. The results suggest an important role for AXL in HFpEF, supporting sAXL evaluation in larger clinical studies and pointing to AXL as a potential target for HF therapy.

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Innate Immune Responses in Transplant Immunity

Ladowski,

Luo

2023

Curr Transpl Rep

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Bone marrow-derived AXL tyrosine kinase promotes mitogenic crosstalk and cardiac allograft vasculopathy

Cited by 4 publications

References 43 publications

Noninvasive methods to reduce cardiac complications postheart transplant

Noninvasive methods to reduce cardiac complications postheart transplant

Prognostic Value of Soluble AXL in Serum from Heart Failure Patients with Preserved and Reduced Left Ventricular Ejection Fraction

Innate Immune Responses in Transplant Immunity

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