Targeting Myeloid-Specific Integrin α9β1 Improves Short- and Long-Term Stroke Outcomes in Murine Models With Preexisting Comorbidities by Limiting Thrombosis and Inflammation

Dhanesha, Nirav; Jain, Manish; Tripathi, Amit Kumar; Doddapattar, Prakash; Chorawala, Mehul R.; Bathla, Girish; Nayak, Manasa K.; Ghatge, Madankumar; Lentz, Steven R.; Kawa, Shigeyuki; Chauhan, Anil K.

doi:10.1161/circresaha.120.316659

Cited by 36 publications

(30 citation statements)

References 49 publications

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“…Integrin α9β1 plays a role in adhesion and transendothelial migration of peripheral neutrophils, hence promoting inflammatory processes. In context of stroke, impairing the function of integrin α9β1 led to reduced thrombosis and inflammation and limited short- and long-term brain damage [ 10 ]. Svep1 and integrin β1-pathways are also involved in maintaining vascular integrity.…”

Section: Introductionmentioning

confidence: 99%

Functional investigation of the coronary artery disease gene SVEP1

et al. 2020

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A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE−/−Svep1+/−) compared to Svep1 wild-type mice (ApoE−/−Svep1+/+) and ApoE−/−Svep1+/− mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE−/−Svep1+/− mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE−/−Svep1+/− mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.

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Section: Introductionmentioning

confidence: 99%

Functional investigation of the coronary artery disease gene SVEP1

et al. 2020

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“…The mechanisms underlying the association between HAR and sICH after endovascular treatment are not entirely clear, and further studies are warranted. In term of previous researches, inflammation plays an important role in the pathophysiological mechanism of ischemic stroke [ 29 – 32 ]. Oxidative stress and inflammatory activity could lead to blood brain barrier disruption, which may be linked to hemorrhagic transformation after endovascular treatment [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Hypersensitive C-reactive protein-albumin ratio predicts symptomatic intracranial hemorrhage after endovascular therapy in acute ischemic stroke patients

et al. 2021

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Background Approximately 10% of patients would develop symptomatic intracranial hemorrhage (sICH) after endovascular therapy. The aim of our study was to explore the ability of hypersensitive C-reactive protein-albumin ratio (HAR) in predicting sICH after endovascular therapy. Methods From April 2016 to December 2018, 334 consecutive patients with anterior circulation infarction undergoing endovascular therapy were enrolled in our study. sICH was defined using Heidelberg bleeding classification after endovascular therapy. Multiple regression analysis was used to investigate the potential risk factors of sICH after endovascular therapy. We used receiver operating characteristic curve analysis and nomogram analysis to assess the overall discriminative ability of the HAR in predicting sICH after endovascular therapy. Results Among these 334 patients enrolled, 37 (11.1%) patients with anterior circulation infarction were identified with sICH after endovascular therapy. Univariate logistic regression analysis demonstrated that patients with higher levels of HAR may be inclined to develop sICH (odds ratio, 10.994; 95% confidence interval, 4.567–26.463; P = 0.001). This association remained significant even after adjustment for potential confounders. Also, a cutoff value of 0.526× 10− 3 for HAR was detected in predicting sICH (area under curve, 0.763). Furthermore, nomogram analysis also suggested that HAR was an indicator of sICH (c-index was 0.890, P< 0.001). Conclusions This study showed that high levels of HAR could predict sICH after endovascular therapy.

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“…The mechanisms underlying the association between HAR and sICH after endovascular treatment are not total clear, and further studies are warranted. In term of previous researches, in ammation plays an important role in the pathophysiological mechanism of ischemic stroke [30][31][32][33] . Oxidative stress and in ammatory activity could lead to blood brain barrier disruption, which may be linked to hemorrhagic transformation after endovascular treatment [34] .…”

Section: Discussionmentioning

confidence: 99%

Hypersensitive C-Reactive Protein-Albumin Ratio Predicts Symptomatic Intracranial Hemorrhage After Endovascular Therapy in Acute Ischemic Stroke Patients

Peng¹,

Hou²,

Wang³

et al. 2020

Preprint

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Background and purpose: A fraction of patients would develop symptomatic intracranial hemorrhage (sICH) after endovascular therapy. The aim of our study was to explore the ability of hypersensitive C-reactive protein-albumin ratio (HAR) in predicting sICH after endovascular therapy.Methods: From April 2016 to December 2018, 334 consecutive patients with anterior circulation infarction undergoing endovascular therapy were enrolled in our study. sICH was defined as a National Institutes of Health Stroke Scale score increase of ≥ 4 points within 24 hours after endovascular therapy. Multiple regression analysis was used to investigate the potential risk factors of sICH after endovascular therapy. We used receiver operating characteristic curve analysis and nomogram analysis to assess the overall discriminative ability of the HAR in predicting sICH after endovascular therapy.Results: Among these 334 patients enrolled, 37 (11.1%) patients with anterior circulation infarction were identified with sICH after endovascular therapy. Univariate logistic regression analysis demonstrated that patients with higher levels of HAR may be inclined to develop sICH [odds ratio, 10.994; 95% confidence interval (CI), 4.567–26.463; P = 0.001]. This association remained significant even after adjustment for potential confounders. Also, a cutoff value of 0.526×10-3 for HAR was detected in predicting sICH (area under curve, 0.763). Furthermore, nomogram analysis also suggested that HAR was an indicator of sICH (c-index was 0.890, P<0.001).Conclusions: This study showed that high levels of HAR may predict sICH after endovascular therapy.

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Targeting Myeloid-Specific Integrin α9β1 Improves Short- and Long-Term Stroke Outcomes in Murine Models With Preexisting Comorbidities by Limiting Thrombosis and Inflammation

Cited by 36 publications

References 49 publications

Functional investigation of the coronary artery disease gene SVEP1

Functional investigation of the coronary artery disease gene SVEP1

Hypersensitive C-reactive protein-albumin ratio predicts symptomatic intracranial hemorrhage after endovascular therapy in acute ischemic stroke patients

Hypersensitive C-Reactive Protein-Albumin Ratio Predicts Symptomatic Intracranial Hemorrhage After Endovascular Therapy in Acute Ischemic Stroke Patients

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