Chao Yang
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Chao Yang has a total of 89 co-authors. Here are the top co-authors by number of shared publications:
Xiaoyu Qi
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
7 shared publicationsPeng Zhou
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
5 shared publications- Yiqing Li
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
5 shared publications Qin Li
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
4 shared publications- Qin Li
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
4 shared publications Fei Cai
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3 shared publications
Latest Publications
- Open Access
- 29 October 2026
- Published by Frontiers Media SA in Frontiers in Bioengineering and Biotechnology
- Vol. 14, 1945232
Serial computed tomography angiography-based computational fluid dynamics characterizes reduced near-renal tear exchange in kidneys that develop atrophy after aortic dissection repair
Background: Renal atrophy may develop after aortic dissection repair despite an anatomically patent renal artery on computed tomography angiography (CTA). This exploratory study compared serial near-renal aortic hemodynamics between kidneys with and without later renal-volume loss. Methods: Six index kidneys from six men were studied: three with ≥30% loss of reference volume (atrophy group) and three age-matched comparators. Patient-specific computational fluid dynamics (CFD) models were built from preoperative, early postoperative and late follow-up CTA; within each patient, inlet and outlet (three-element Windkessel) boundary conditions were identical across time points. All 90 true-lumen/false-lumen (TL/FL) communications were characterized by distance from the renal-ostial plane, direction, pressure difference and trans-tear flow. TL/FL relationships were quantified at the renal-ostial plane, and bilateral renal-artery flow was computed directly. Renal volume was measured by three-dimensional CTA segmentation. Results: All six index kidneys were supplied from the FL before repair. Index-kidney volume changed by −53.0%, −64.1% and −50.6% in the atrophy group and by −13.8%, +0.8% and −10.7% in comparators. No hemodynamic measure separated the groups before repair. From the early postoperative model onward (3–37 days), two aortic-level flow measures were lower in every atrophy kidney than in every comparator: the FL flow-magnitude fraction at the renal-ostial plane (0.03–0.10 versus 0.13–0.79) and total peak-systolic trans-communication flow (37.8–45.1 versus 61.8–185.3 mL/s). Index renal-artery flow separated the groups only at late follow-up (−29.4%, −32.6% and −63.9% versus +5.9%, −7.4% and −3.0%), as did tear-exchange flow directed toward the renal-ostial level (1.9–19.1 versus 38.7–130.9 mL/s). FL/TL pressure ratios did not separate the groups at any time point. In one patient-derived geometry, sequential virtual closure of idealized communications redistributed and reversed flow in the remaining communications; index renal-artery flow after the final closure was similar to baseline. Conclusion: In kidneys that later atrophied, the FL flow contribution at the renal level was lower than in comparators early after repair, before the modeled decrease in renal-artery flow and, in two of three kidneys, before substantial volume loss. Given three kidneys per group and multiple measures, these associations are hypothesis-generating and do not establish causation, renal parenchymal perfusion or a treatment threshold.
- 29 October 2026
- Published by Frontiers Media SA in Frontiers in Bioengineering and Biotechnology
- Vol. 14, 1945232
Open AccessSerial computed tomography angiography-based computational fluid dynamics characterizes reduced near-renal tear exchange in kidneys that develop atrophy after aortic dissection repair
Background: Renal atrophy may develop after aortic dissection repair despite an anatomically patent renal artery on computed tomography angiography (CTA). This exploratory study compared serial near-renal aortic hemodynamics between kidneys with and without later renal-volume loss. Methods: Six index kidneys from six men were studied: three with ≥30% loss of reference volume (atrophy group) and three age-matched comparators. Patient-specific computational fluid dynamics (CFD) models were built from preoperative, early postoperative and late follow-up CTA; within each patient, inlet and outlet (three-element Windkessel) boundary conditions were identical across time points. All 90 true-lumen/false-lumen (TL/FL) communications were characterized by distance from the renal-ostial plane, direction, pressure difference and trans-tear flow. TL/FL relationships were quantified at the renal-ostial plane, and bilateral renal-artery flow was computed directly. Renal volume was measured by three-dimensional CTA segmentation. Results: All six index kidneys were supplied from the FL before repair. Index-kidney volume changed by −53.0%, −64.1% and −50.6% in the atrophy group and by −13.8%, +0.8% and −10.7% in comparators. No hemodynamic measure separated the groups before repair. From the early postoperative model onward (3–37 days), two aortic-level flow measures were lower in every atrophy kidney than in every comparator: the FL flow-magnitude fraction at the renal-ostial plane (0.03–0.10 versus 0.13–0.79) and total peak-systolic trans-communication flow (37.8–45.1 versus 61.8–185.3 mL/s). Index renal-artery flow separated the groups only at late follow-up (−29.4%, −32.6% and −63.9% versus +5.9%, −7.4% and −3.0%), as did tear-exchange flow directed toward the renal-ostial level (1.9–19.1 versus 38.7–130.9 mL/s). FL/TL pressure ratios did not separate the groups at any time point. In one patient-derived geometry, sequential virtual closure of idealized communications redistributed and reversed flow in the remaining communications; index renal-artery flow after the final closure was similar to baseline. Conclusion: In kidneys that later atrophied, the FL flow contribution at the renal level was lower than in comparators early after repair, before the modeled decrease in renal-artery flow and, in two of three kidneys, before substantial volume loss. Given three kidneys per group and multiple measures, these associations are hypothesis-generating and do not establish causation, renal parenchymal perfusion or a treatment threshold.
- Open Access
- 15 September 2026
- Published by Frontiers Media SA in Frontiers in Bioengineering and Biotechnology
- Vol. 14, 1901373
Impact of stent graft geometry on hemodynamics in superior mesenteric artery reconstruction after fenestrated/branched endovascular aneurysm repair
Background: During visceral artery reconstruction in fenestrated/branched endovascular aneurysm repair (F/B-EVAR), the superior mesenteric artery (SMA) plays a critical role in intestinal perfusion and often exhibits complex postoperative geometry. In this study, we employed computational fluid dynamics (CFD) with virtual modeling to simulate various SMA reconstruction strategies and systematically evaluate the impact of postoperative geometric configurations on SMA hemodynamics. Methods: Virtual parametric models representing 12 postoperative geometric configurations were artificially reconstructed from CTA images. Proximal parameters of the superior mesenteric artery stent, including the stent graft inflow angle (θ) and intraluminal length-to-aortic diameter ratio (L/D), as well as the distal parameter, the outlet angle (α), were defined to differentiate these 12 configurations. Hemodynamic parameters Pressure ratio (the SMA outlet pressure/descending aortic inlet pressure), flow fraction (branch flow/total aortic inflow), and hemodynamic indices, including time-averaged wall shear stress and oscillatory shear index were defined to evaluate hemodynamic differences across the configurations. Results: PR decreased up to 5.2% for maximum as θ increased. Retrograde configurations (θ > 90°) generated inlet vortices during deceleration, most pronounced at θ = 180°. Variation in L/D did not produce a meaningful change in PR, whereas increasing L/D was associated with a more pronounced local flow disturbance beneath the protruding segment. Vortical structures formed beneath stent segments protruding into the aorta during systole, with vortex size positively correlated with L/D and more pronounced during systolic deceleration. PR values were similar among models with different α configurations. But hemodynamic indices indicated that a larger outlet angle α conferred greater benefits to the endothelial environment. The patient-specific illustrations showed consistency with these findings. Conclusion: This study elucidates the hemodynamic consequences of varying SMA stent graft configurations during F/B-EVAR and provides biomechanical insights to aid optimal clinical decision-making for SMA stent graft positioning.
- 15 September 2026
- Published by Frontiers Media SA in Frontiers in Bioengineering and Biotechnology
- Vol. 14, 1901373
Open AccessImpact of stent graft geometry on hemodynamics in superior mesenteric artery reconstruction after fenestrated/branched endovascular aneurysm repair
Background: During visceral artery reconstruction in fenestrated/branched endovascular aneurysm repair (F/B-EVAR), the superior mesenteric artery (SMA) plays a critical role in intestinal perfusion and often exhibits complex postoperative geometry. In this study, we employed computational fluid dynamics (CFD) with virtual modeling to simulate various SMA reconstruction strategies and systematically evaluate the impact of postoperative geometric configurations on SMA hemodynamics. Methods: Virtual parametric models representing 12 postoperative geometric configurations were artificially reconstructed from CTA images. Proximal parameters of the superior mesenteric artery stent, including the stent graft inflow angle (θ) and intraluminal length-to-aortic diameter ratio (L/D), as well as the distal parameter, the outlet angle (α), were defined to differentiate these 12 configurations. Hemodynamic parameters Pressure ratio (the SMA outlet pressure/descending aortic inlet pressure), flow fraction (branch flow/total aortic inflow), and hemodynamic indices, including time-averaged wall shear stress and oscillatory shear index were defined to evaluate hemodynamic differences across the configurations. Results: PR decreased up to 5.2% for maximum as θ increased. Retrograde configurations (θ > 90°) generated inlet vortices during deceleration, most pronounced at θ = 180°. Variation in L/D did not produce a meaningful change in PR, whereas increasing L/D was associated with a more pronounced local flow disturbance beneath the protruding segment. Vortical structures formed beneath stent segments protruding into the aorta during systole, with vortex size positively correlated with L/D and more pronounced during systolic deceleration. PR values were similar among models with different α configurations. But hemodynamic indices indicated that a larger outlet angle α conferred greater benefits to the endothelial environment. The patient-specific illustrations showed consistency with these findings. Conclusion: This study elucidates the hemodynamic consequences of varying SMA stent graft configurations during F/B-EVAR and provides biomechanical insights to aid optimal clinical decision-making for SMA stent graft positioning.
- Open Access
- 29 December 2025
- Published by Springer Nature in Molecular Biomedicine
- Vol. 6 (1) , 150
Activated oligoadenylate synthetase-ribonuclease L pathway promotes endothelial pyroptosis and impairs diabetic wound healing via thioredoxin-interacting protein m6A methylation
In diabetic skin, even in the absence of infection, the antiviral enzymes 2′-5′-oligoadenylate synthetase (OAS) and ribonuclease L (RNase L) demonstrate abnormally heightened activity. This dysregulation triggers a state of cellular stress, which not only suppresses intracellular protein synthesis but also activates innate immune responses—particularly upon pathogenic bacterial invasion. Whether the sustained activation of the OAS–RNase L pathway in diabetic skin tissue critically contributes to impaired wound healing remains to be determined. We have investigated the pyroptosis changes in human umbilical vein endothelial cells (HUVECs) treated with Lipopolysaccharide (LPS) under high glucose by RNase L small interfering RNA (siRNA) to down-regulate RNase L expression. Under high glucose conditions, we observed abnormal activation of the OAS/RNase L pathway in HUVECs, which further exacerbated cellular pyroptosis upon LPS stimulation. Abnormally activated RNase L, which reduces the expression of methyltransferase 3 (METTL3), led to decreased m 6 A methylation of thioredoxin-interacting protein mRNA (TXNIP mRNA). The decreased degradation of TXNIP mRNA by the hypomethylation leads to increased TXNIP expression, which in turn enhances pyroptosis.. In vitro experiments, the impact of RNase L inhibitor Ellagic acid (EA) on diabetic wound healing in STZ (streptozotocin)-induced diabetic mice was evaluated. We found a reduction in skin pyroptosis and improved wound healing when EA was administered orally. Our results demonstrate that hyperglycemia-induced OAS/RNase L activation increases endothelial cell susceptibility to pyroptosis and inflammatory responses during infection. These findings provide valuable insights for developing novel therapeutic strategies for diabetic wound management.
- 29 December 2025
- Published by Springer Nature in Molecular Biomedicine
- Vol. 6 (1) , 150
Open AccessActivated oligoadenylate synthetase-ribonuclease L pathway promotes endothelial pyroptosis and impairs diabetic wound healing via thioredoxin-interacting protein m6A methylation
In diabetic skin, even in the absence of infection, the antiviral enzymes 2′-5′-oligoadenylate synthetase (OAS) and ribonuclease L (RNase L) demonstrate abnormally heightened activity. This dysregulation triggers a state of cellular stress, which not only suppresses intracellular protein synthesis but also activates innate immune responses—particularly upon pathogenic bacterial invasion. Whether the sustained activation of the OAS–RNase L pathway in diabetic skin tissue critically contributes to impaired wound healing remains to be determined. We have investigated the pyroptosis changes in human umbilical vein endothelial cells (HUVECs) treated with Lipopolysaccharide (LPS) under high glucose by RNase L small interfering RNA (siRNA) to down-regulate RNase L expression. Under high glucose conditions, we observed abnormal activation of the OAS/RNase L pathway in HUVECs, which further exacerbated cellular pyroptosis upon LPS stimulation. Abnormally activated RNase L, which reduces the expression of methyltransferase 3 (METTL3), led to decreased m 6 A methylation of thioredoxin-interacting protein mRNA (TXNIP mRNA). The decreased degradation of TXNIP mRNA by the hypomethylation leads to increased TXNIP expression, which in turn enhances pyroptosis.. In vitro experiments, the impact of RNase L inhibitor Ellagic acid (EA) on diabetic wound healing in STZ (streptozotocin)-induced diabetic mice was evaluated. We found a reduction in skin pyroptosis and improved wound healing when EA was administered orally. Our results demonstrate that hyperglycemia-induced OAS/RNase L activation increases endothelial cell susceptibility to pyroptosis and inflammatory responses during infection. These findings provide valuable insights for developing novel therapeutic strategies for diabetic wound management.
- Open Access
- 13 November 2025
- Published by Frontiers Media SA in Frontiers in Bioengineering and Biotechnology
- Vol. 13, 1640687
Estimating flow division in aortic branches of diseased aorta: a method for boundary condition specification in CFD analysis
Hemodynamic predictions using computational fluid dynamics (CFD) simulations can provide valuable guidance assessing aortic disease risks. However, their reliability is hindered by the lack of patient-specific boundary conditions, particularly measured flow rates. This study addresses this knowledge gap by introducing a method for estimating flow division in aortic branches. The geometry of the lesional aorta was first repaired to obtain a near-healthy reference geometry. An iterative CFD simulation was then employed to estimate the flow division in the branches of the diseased aorta. Specifically, empirical boundary conditions from healthy individuals were used to predict the outlet pressures of reference geometry, which were subsequently converted into resistance models. These resistance models were then assigned to the outlets of the diseased aorta to predict the inlet pressure. The discrepancy between the predicted and target inlet pressures was iteratively minimized by adjusting the inlet pressure of the reference model until convergence was achieved. The final flow division in the branches of the diseased aorta was then obtained. The performance of the proposed method was investigated in three patients with aortic dissection or aneurysm. The proposed method predicted lower flow rates in branches with severe stenosis, which was more consistent with physiological expectations. Furthermore, the predicted blood pressure differed significantly from that obtained using the traditional method and was closer to the target values. The proposed method provides a practical solution for specifying boundary conditions in hemodynamic studies when clinically measured flow rates are unavailable.
- 13 November 2025
- Published by Frontiers Media SA in Frontiers in Bioengineering and Biotechnology
- Vol. 13, 1640687
Open AccessEstimating flow division in aortic branches of diseased aorta: a method for boundary condition specification in CFD analysis
Hemodynamic predictions using computational fluid dynamics (CFD) simulations can provide valuable guidance assessing aortic disease risks. However, their reliability is hindered by the lack of patient-specific boundary conditions, particularly measured flow rates. This study addresses this knowledge gap by introducing a method for estimating flow division in aortic branches. The geometry of the lesional aorta was first repaired to obtain a near-healthy reference geometry. An iterative CFD simulation was then employed to estimate the flow division in the branches of the diseased aorta. Specifically, empirical boundary conditions from healthy individuals were used to predict the outlet pressures of reference geometry, which were subsequently converted into resistance models. These resistance models were then assigned to the outlets of the diseased aorta to predict the inlet pressure. The discrepancy between the predicted and target inlet pressures was iteratively minimized by adjusting the inlet pressure of the reference model until convergence was achieved. The final flow division in the branches of the diseased aorta was then obtained. The performance of the proposed method was investigated in three patients with aortic dissection or aneurysm. The proposed method predicted lower flow rates in branches with severe stenosis, which was more consistent with physiological expectations. Furthermore, the predicted blood pressure differed significantly from that obtained using the traditional method and was closer to the target values. The proposed method provides a practical solution for specifying boundary conditions in hemodynamic studies when clinically measured flow rates are unavailable.
- 24 May 2025
- Published by Elsevier in International Immunopharmacology
- Vol. 159, 114899
GDF15 suppresses abdominal aortic aneurysm by upregulating AREG expression to adjust macrophage polarization
- 24 May 2025
- Published by Elsevier in International Immunopharmacology
- Vol. 159, 114899
GDF15 suppresses abdominal aortic aneurysm by upregulating AREG expression to adjust macrophage polarization
- Open Access
- 1 April 2025
- Published by AME Publishing Company in AME Case Reports
- Vol. 9, 54
Retrograde growing intravenous leiomyomatosis—a case report
Case Report Retrograde growing intravenous leiomyomatosis—a case report Jinrong Xiong, Shan Zhang, Wanying Wu, Peng Zhou, Xiaoyu Qi, Gezheng Chen, Fei Cai, Binbin Long, Qin Li, Chao Yang
- 1 April 2025
- Published by AME Publishing Company in AME Case Reports
- Vol. 9, 54
Open AccessRetrograde growing intravenous leiomyomatosis—a case report
Case Report Retrograde growing intravenous leiomyomatosis—a case report Jinrong Xiong, Shan Zhang, Wanying Wu, Peng Zhou, Xiaoyu Qi, Gezheng Chen, Fei Cai, Binbin Long, Qin Li, Chao Yang
- Open Access
- 25 October 2024
- Published by Wiley in Advanced Science
- Vol. 11 (47) , e2400653
Regional Stiffness and Hardening Indices: New Indicators Derived from Multidimensional Dynamic CTA for Aneurysm Risk Assessment
Two indices, indicating the regional average stiffness and the pace of strain hardening respectively, are derived from the nonlinear stress–strain behavior obtained from biomechanical analysis of aneurysm. A comprehensive method based on electrocardiographic‐gated multidimensional dynamic computed tomography angiography (MD CTA) is developed for extracting these mechanical characteristics in vivo. The proposed indices are evaluated by 26 cases including 9 healthy, one aortosclerosis, and 16 abdominal aortic aneurysm cases. The difference of SSI and dSSI value between aneurysmal and healthy groups is up to orders in magnitude. Significant correlation of these indices with the clinical indicator of aneurysm diameter is found. Logistic models based on these indices are capable to sharply discriminate the healthy and the aneurysmal arteries with AUC>0.98. This work introduces new tools and new indices for aortic mechanical assessment which may shed light on understanding the mechanical condition, pathological state and eventually benefit clinical decision‐making.
- 25 October 2024
- Published by Wiley in Advanced Science
- Vol. 11 (47) , e2400653
Open AccessRegional Stiffness and Hardening Indices: New Indicators Derived from Multidimensional Dynamic CTA for Aneurysm Risk Assessment
Two indices, indicating the regional average stiffness and the pace of strain hardening respectively, are derived from the nonlinear stress–strain behavior obtained from biomechanical analysis of aneurysm. A comprehensive method based on electrocardiographic‐gated multidimensional dynamic computed tomography angiography (MD CTA) is developed for extracting these mechanical characteristics in vivo. The proposed indices are evaluated by 26 cases including 9 healthy, one aortosclerosis, and 16 abdominal aortic aneurysm cases. The difference of SSI and dSSI value between aneurysmal and healthy groups is up to orders in magnitude. Significant correlation of these indices with the clinical indicator of aneurysm diameter is found. Logistic models based on these indices are capable to sharply discriminate the healthy and the aneurysmal arteries with AUC>0.98. This work introduces new tools and new indices for aortic mechanical assessment which may shed light on understanding the mechanical condition, pathological state and eventually benefit clinical decision‐making.
- Open Access
- 7 February 2024
- Published by Wolters Kluwer Health in Chinese Medical Journal
- Vol. 137 (6) , 752-754
Current status and future development of aortic stent fenestration-assisted techniques
- 7 February 2024
- Published by Wolters Kluwer Health in Chinese Medical Journal
- Vol. 137 (6) , 752-754
Open AccessCurrent status and future development of aortic stent fenestration-assisted techniques
- 28 December 2023
- Published by Springer Nature in Current Medical Science
- Vol. 43 (6) , 1221-1228
Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy
Objective This study aimed to investigate the safety and efficacy of endovascular aortic repair (EVAR) for the treatment of an abdominal aortic aneurysm (AAA) with a hostile neck anatomy (HNA). Methods From January 1, 2015 to December 31, 2019, a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study. Based on the morphological characteristics of the proximal neck anatomy, the patients were divided into the HNA group and the friendly neck anatomy (FNA) group. The patients were followed up for up to 4 years. Results The average follow-up time was 1056.1±535.5 days. Type I endoleak occurred in 4 patients in the HNA group, and 2 patients in the FNA group. Neither death nor intraoperative switch to open repair occurred in either group. The time of the operation was significantly longer in the HNA group (FNA vs. HNA, 99.2±51.1 min vs. 117.5±63.8 min, P=0.011). There were no significant differences in short-term clinical success rate (P=0.228) or midterm clinical success rate (P=0.889) between the two groups. The overall mortality rate was 10.4%, and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period (P=0.889). Conclusion EVAR was feasible and safe in patients with an AAA with a proximal HNA. The early and midterm results were promising; however, further studies are needed to verify the long-term effectiveness of EVAR.
- 28 December 2023
- Published by Springer Nature in Current Medical Science
- Vol. 43 (6) , 1221-1228
Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy
Objective This study aimed to investigate the safety and efficacy of endovascular aortic repair (EVAR) for the treatment of an abdominal aortic aneurysm (AAA) with a hostile neck anatomy (HNA). Methods From January 1, 2015 to December 31, 2019, a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study. Based on the morphological characteristics of the proximal neck anatomy, the patients were divided into the HNA group and the friendly neck anatomy (FNA) group. The patients were followed up for up to 4 years. Results The average follow-up time was 1056.1±535.5 days. Type I endoleak occurred in 4 patients in the HNA group, and 2 patients in the FNA group. Neither death nor intraoperative switch to open repair occurred in either group. The time of the operation was significantly longer in the HNA group (FNA vs. HNA, 99.2±51.1 min vs. 117.5±63.8 min, P=0.011). There were no significant differences in short-term clinical success rate (P=0.228) or midterm clinical success rate (P=0.889) between the two groups. The overall mortality rate was 10.4%, and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period (P=0.889). Conclusion EVAR was feasible and safe in patients with an AAA with a proximal HNA. The early and midterm results were promising; however, further studies are needed to verify the long-term effectiveness of EVAR.
- Open Access
- 27 December 2023
- Published by MDPI AG in Biomolecules
- Vol. 14 (1) , 38
GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex
Growth differentiation factor-15 (GDF-15) is proposed to be strongly associated with several cardiovascular diseases, such as heart failure and atherosclerosis. Moreover, some recent studies have reported an association between GDF-15 and platelet activation. In this study, we isolated peripheral blood platelets from healthy volunteers and evaluated the effect of GDF-15 on adenosine diphosphate (ADP)-induced platelet activation using the platelet aggregation assay. Subsequently, we detected the expression of GDF-15-related receptors on platelets, including the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), transforming growth factor-beta receptor I (TGF-βRI), transforming growth factor-beta receptor II (TGF-βRII), glial-cell-line-derived neurotrophic factor family receptor α-like (GFRAL), and those rearranged during transfection (RET). Then, we screened for GDF-15 receptors using the GDF-15-related receptor microarray comprising these recombinant proteins. We also performed the immunoprecipitation assay to investigate the interaction between GDF-15 and the receptors on platelets. For the further exploration of signaling pathways, we investigated the effects of GDF-15 on the extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and Janus kinase 2 (JAK2) pathways. We also investigated the effects of GDF-15 on the ERK and AKT pathways and platelet aggregation in the presence or absence of RET agonists or inhibition. Our study revealed that GDF-15 can dose-independently inhibit ADP-induced human platelet aggregation and that the binding partner of GDF-15 on platelets is GFRAL. We also found that GDF-15 inhibits ADP-induced AKT and ERK activation in platelets. Meanwhile, our results revealed that the inhibitory effects of GDF-15 can be mediated by the GFRAL/RET complex. These findings reveal the novel inhibitory mechanism of ADP-induced platelet activation by GDF-15.
- 27 December 2023
- Published by MDPI AG in Biomolecules
- Vol. 14 (1) , 38
Open AccessGDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex
Growth differentiation factor-15 (GDF-15) is proposed to be strongly associated with several cardiovascular diseases, such as heart failure and atherosclerosis. Moreover, some recent studies have reported an association between GDF-15 and platelet activation. In this study, we isolated peripheral blood platelets from healthy volunteers and evaluated the effect of GDF-15 on adenosine diphosphate (ADP)-induced platelet activation using the platelet aggregation assay. Subsequently, we detected the expression of GDF-15-related receptors on platelets, including the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), transforming growth factor-beta receptor I (TGF-βRI), transforming growth factor-beta receptor II (TGF-βRII), glial-cell-line-derived neurotrophic factor family receptor α-like (GFRAL), and those rearranged during transfection (RET). Then, we screened for GDF-15 receptors using the GDF-15-related receptor microarray comprising these recombinant proteins. We also performed the immunoprecipitation assay to investigate the interaction between GDF-15 and the receptors on platelets. For the further exploration of signaling pathways, we investigated the effects of GDF-15 on the extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and Janus kinase 2 (JAK2) pathways. We also investigated the effects of GDF-15 on the ERK and AKT pathways and platelet aggregation in the presence or absence of RET agonists or inhibition. Our study revealed that GDF-15 can dose-independently inhibit ADP-induced human platelet aggregation and that the binding partner of GDF-15 on platelets is GFRAL. We also found that GDF-15 inhibits ADP-induced AKT and ERK activation in platelets. Meanwhile, our results revealed that the inhibitory effects of GDF-15 can be mediated by the GFRAL/RET complex. These findings reveal the novel inhibitory mechanism of ADP-induced platelet activation by GDF-15.