scholarly journals The Incremental Prognostic Value of Hepatocyte Growth Factor in First-Ever Acute Ischemic Stroke: An Early Link Between Growth Factor and Interleukins

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangfang Li ◽  
Ping Liu ◽  
Yuyou Huang ◽  
Lingzhi Li ◽  
Sijia Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Acute Ischemic Stroke ◽  
Predictive Accuracy ◽  
Characteristic Curve ◽  
Stroke Outcome ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) is a potential prognostic factor for acute ischemic stroke (AIS). In this study, we sought to validate its earlier predictive accuracy within 24 h for first-ever AIS. Moreover, as HGF interacts with interleukins, their associations may lead to novel immunomodulatory therapeutic strategies. Patients with first-ever AIS (n = 202) within 24 h were recruited. Plasma HGF and related interleukin concentrations were measured by multiplex immunoassays. The primary and secondary outcomes were major disability (modified Rankin scale score ≥3) at 3 months after AIS and death, respectively. Elastic net regression was applied to screen variables associated with stroke outcome; binary multivariable logistic analysis was then used to explore the relationship between HGF level and stroke outcome. After multivariate adjustment, upregulated HGF levels were associated with an increased risk of the primary outcome (odds ratio, 7.606; 95% confidence interval, 3.090–18.726; p < 0.001). Adding HGF to conventional risk factors significantly improved the predictive power for unfavorable outcomes (continuous net reclassification improvement 37.13%, p < 0.001; integrated discrimination improvement 8.71%, p < 0.001). The area under the receiver operating characteristic curve value of the traditional model was 0.8896 and reached 0.9210 when HGF was introduced into the model. An elevated HGF level may also be a risk factor for mortality within 3 months poststroke. The HGF level was also positively correlated with IL-10 and IL-16 levels, and HGF before interaction with all interleukins was markedly negatively correlated with the lymphocyte/neutrophil ratio. HGF within 24 h may have prognostic potential for AIS. Our findings reinforce the link between HGF and interleukins.

scholarly journals Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of Acute Ischemic Stroke

Stroke ◽  
2018 ◽  
Vol 49 (2) ◽  
pp. 377-383 ◽  
Author(s):  
Zhengbao Zhu ◽  
Tan Xu ◽  
Daoxia Guo ◽  
Xinfeng Huangfu ◽  
Chongke Zhong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Acute Ischemic Stroke ◽  
Hepatocyte Growth

scholarly journals Assessing the Relative Value of CT Perfusion Compared to Non-contrast CT and CT Angiography in Prognosticating Reperfusion-Eligible Acute Ischemic Stroke Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrew Bivard ◽  
Christopher Levi ◽  
Longting Lin ◽  
Xin Cheng ◽  
Richard Aviv ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Ct Angiography ◽  
Predictive Accuracy ◽  
Ct Perfusion ◽  
Imaging Modality ◽  
Characteristic Curve ◽  
Treatment Decision ◽  
Receiver Operator Characteristic Curve ◽  
Stroke Patients

In the present study we sought to measure the relative statistical value of various multimodal CT protocols at identifying treatment responsiveness in patients being considered for thrombolysis. We used a prospectively collected cohort of acute ischemic stroke patients being assessed for IV-alteplase, who had CT-perfusion (CTP) and CT-angiography (CTA) before a treatment decision. Linear regression and receiver operator characteristic curve analysis were performed to measure the prognostic value of models incorporating each imaging modality. One thousand five hundred and sixty-two sub-4.5 h ischemic stroke patients were included in this study. A model including clinical variables, alteplase treatment, and NCCT ASPECTS was weak (R2 0.067, P < 0.001, AUC 0.605) at predicting 90 day mRS. A second model, including dynamic CTA variables (collateral grade, occlusion severity) showed better predictive accuracy for patient outcome (R2 0.381, P < 0.001, AUC 0.781). A third model incorporating CTP variables showed very high predictive accuracy (R2 0.488, P < 0.001, AUC 0.899). Combining all three imaging modalities variables also showed good predictive accuracy for outcome but did not improve on the CTP model (R2 0.439, P < 0.001, AUC 0.825). CT perfusion predicts patient outcomes from alteplase therapy more accurately than models incorporating NCCT and/or CT angiography. This data has implications for artificial intelligence or machine learning models.

scholarly journals Sustained Functional Improvement by Hepatocyte Growth Factor-Like Small Molecule BB3 after Focal Cerebral Ischemia in Rats and Mice

2015 ◽  
Vol 35 (6) ◽  
pp. 1044-1053 ◽  
Author(s):  
Rafael E Chaparro ◽  
Miwa Izutsu ◽  
Toshihiro Sasaki ◽  
Huaxin Sheng ◽  
Yi Zheng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Small Molecule ◽  
Artery Occlusion ◽  
Neurologic Function ◽  
Cerebral Artery Occlusion ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF), efficacious in preclinical models of acute central nervous system injury, is burdened by administration of full-length proteins. A multiinstitutional consortium investigated the efficacy of BB3, a small molecule with HGF-like activity that crosses the blood-brain barrier in rodent focal ischemic stroke using Stroke Therapy Academic Industry Roundtable (STAIR) and Good Laboratory Practice guidelines. In rats, BB3, begun 6 hours after temporary middle cerebral artery occlusion (tMCAO) reperfusion, or permanent middle cerebral artery occlusion (pMCAO) onset, and continued for 14 days consistently improved long-term neurologic function independent of sex, age, or laboratory. BB3 had little effect on cerebral infarct size and no effect on blood pressure. BB3 increased HGF receptor c-Met phosphorylation and synaptophysin expression in penumbral tissue consistent with a neurorestorative mechanism from HGF-like activity. In mouse tMCAO, BB3 starting 10 minutes after reperfusion and continued for 14 days improved neurologic function that persisted for 8 weeks in some, but not all measures. Study in animals with comorbidities and those exposed to common stroke drugs are the next steps to complete preclinical assessment. These data, generated in independent, masked, and rigorously controlled settings, are the first to suggest that the HGF pathway can potentially be harnessed by BB3 for neurologic benefit after ischemic stroke.

Abstract P143: Circulating Level of Hepatocyte Growth Factor and Incidence of Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Michael P Bancks ◽  
Suzette J Bielinski ◽  
Paul A Decker ◽  
Naomi Q Hanson ◽  
Nicholas B Larson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cox Regression ◽  
Fasting Glucose ◽  
Smoking Status ◽  
Incident Diabetes ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Race Ethnicity ◽  
Hepatocyte Growth

Introduction: Increased levels of hepatocyte growth factor (HGF), active in cell growth, motility, and morphogenesis, are associated with the presence of obesity, poor metabolic health, and cardiovascular disease. Hypothesis: We assessed the hypothesis that higher baseline levels of HGF will be associated with increased risk of diabetes. Methods: We examined the association between HGF and incident diabetes in MESA, including 5395 men and women 45-84 years of age at enrollment (2000-02). Fasting serum HGF was measured at baseline and on a subsample of participants at exam 2 (n = 1915). From 2000-11, incidence of diabetes was ascertained over 4 follow-up examinations, determined by new use of insulin or oral hypoglycemic medication or fasting glucose ≥ 126 mg/dL. Cox regression was used to estimate hazard ratios (HR) for incident diabetes according to 1 standard deviation unit (SDU) of HGF (1 SDU =256 pg/mL), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, BMI, WC, fasting glucose and insulin, CRP, and IL-6 levels. Similarly, hazard ratios for incident diabetes were estimated according to change in HGF levels from exam 1 to exam 2 in the subsample. Results: At baseline, older age, male sex, current smoking, and higher body mass index (BMI), waist circumference (WC), fasting glucose and insulin, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were all associated with higher levels of HGF, while greater education and physical activity were associated with lower serum HGF. Incidence of diabetes in this analytic sample was 12% (n cases = 670). Per 1 SDU increase in baseline HGF level, unadjusted risk for diabetes increased 1.46 fold (95% CI=1.37, 1.56). After adjustment, diabetes risk per 1 SDU increase in HGF was attenuated but remained significantly increased (HR=1.22; 95% CI=1.12, 1.32). No association was found between change in HGF level between exam 1 and exam 2 and incidence of diabetes. There was no evidence of effect modification by race/ethnicity for either analysis. Conclusion: In conclusion, in this ethnically diverse U.S. adult population, higher levels of serum HGF were independently associated with increased incidence of diabetes.

scholarly journals Association of Circulating Hepatocyte Growth Factor and Risk of Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis

Angiology ◽  
2020 ◽  
Vol 71 (6) ◽  
pp. 544-551
Author(s):  
Parveen K. Garg ◽  
Petra Buzkova ◽  
Christina L. Wassell ◽  
Matthew Allison ◽  
Michael Criqui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Ethnic Study ◽  
Increased Risk ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
Hepatocyte Growth

Higher levels of hepatocyte growth factor (HGF) have been associated with the presence of peripheral arterial disease (PAD), but prospective associations are unknown. We examined the association of circulating HGF levels with incident PAD. Between 2000 and 2002, HGF was measured in 6742 Multi-Ethnic Study of Atherosclerosis participants without PAD. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015. Incident low ankle-brachial index (ABI), defined as an ABI < 0.9 and a decline of ≥ 0.15, was assessed among 5736 individuals who had an ABI > 0.9 at baseline and ≥1 follow-up ABI measurement 3 to 10 years later. There were 116 clinical PAD and 197 low ABI events that occurred over a median follow-up of 14 and 9 years, respectively. After adjustment for demographic and clinical variables, a standard deviation increment of HGF (303 ng/L) was associated with an increased risk of clinical PAD (hazard ratio: 1.21; 95% confidence interval [CI]: 1.05-1.39) but not a low ABI (rate ratio: 1.03; 95% CI: 0.85-1.25). In conclusion, higher HGF levels were modestly associated with an increased risk of developing clinical PAD.

scholarly journals Hepatocyte Growth Factor and the Risk of Ischemic Stroke Developing Among Postmenopausal Women

Stroke ◽  
2010 ◽  
Vol 41 (5) ◽  
pp. 857-862 ◽  
Author(s):  
Swapnil N. Rajpathak ◽  
Tao Wang ◽  
Sylvia Wassertheil-Smoller ◽  
Howard D. Strickler ◽  
Robert C. Kaplan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Postmenopausal Women ◽  
Hepatocyte Growth

The Association Between Serum Endocan Level and Short-Term Prognosis of Patients With Acute Ischemic Stroke

Angiology ◽  
2021 ◽  
pp. 000331972110307
Author(s):  
Feng Han ◽  
Weifang Liao ◽  
Xunxin Duan ◽  
Yuying Shi ◽  
Zhijian Hu
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Characteristic Curve ◽  
Outcome Data ◽  
Stroke Onset ◽  
Risk Of Death ◽  
Increased Risk ◽  
Potential Prognostic Factor ◽  
Disability Outcome ◽  
Incident Rate

This cohort study was designed to assess the association between serum endocan levels and the prognosis of acute ischemic stroke. A total of 227 patients were recruited consecutively. Study outcome data on death and major disability (modified Rankin Scale score ≥3) were collected at 3 months after stroke onset. After 3 months of follow-up, death and disability occurred in 48 and 85 patients, respectively, while the primary (death) and secondary (death or disability) outcome incident rate was 21.15% and 37.44%, respectively. The multivariable adjusted odds ratio (OR) (95% confidence interval, 95% CIs) of the highest endocan quartile for death or major disability was 1.21 (1.10, 4.13) compared with the lowest quartile. After adjusting for confounding factors, the increase in the risk of death was not significant. Receiver operating characteristic curve analysis showed that endocan predicted primary and secondary outcomes with C-statistical values (95% CIs) of 0.61 (0.55–0.67, P = .001) and 0.68 (0.59–0.76, P < .001), respectively. Elevated endocan levels were independently related to increased risk of poor outcome at 3 months after ischemic stroke onset. Endocan is a potential prognostic factor for ischemic stroke.

scholarly journals Amniotic fluid-borne hepatocyte growth factor protects rat pups against experimental necrotizing enterocolitis

2014 ◽  
Vol 306 (5) ◽  
pp. G361-G369 ◽  
Author(s):  
Sunil K. Jain ◽  
Eric W. Baggerman ◽  
Krishnan MohanKumar ◽  
Kopperuncholan Namachivayam ◽  
Ramasamy Jagadeeswaran ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Amniotic Fluid ◽  
Necrotizing Enterocolitis ◽  
Antibody Array ◽  
Rat Pups ◽  
Increased Risk ◽  
Fluid Supplementation ◽  
Hepatocyte Growth

Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to amniotic fluid-borne growth factors, possibly contributing to the increased risk of necrotizing enterocolitis (NEC) in premature infants. We hypothesized that supplementation of formula feeds with amniotic fluid can provide amniotic fluid-borne growth factors and prevent experimental NEC in rat pups. We compared NEC-like injury in rat pups fed with infant formula vs. formula supplemented either with 30% amniotic fluid or recombinant hepatocyte growth factor (HGF). Cytokines/growth factors in amniotic fluid were measured by immunoassays. Amniotic fluid and HGF effects on enterocyte migration, proliferation, and survival were measured in cultured IEC6 intestinal epithelial cells. Finally, we used an antibody array to investigate receptor tyrosine kinase (RTK) activation and immunoblots to measure phosphoinositide 3-kinase (PI3K) signaling. Amniotic fluid supplementation in oral feeds protected rat pups against NEC-like injury. HGF was the most abundant growth factor in rat amniotic fluid in our panel of analytes. Amniotic fluid increased cell migration, proliferation, and cell survival in vitro. These effects were reproduced by HGF and blocked by anti-HGF antibody or a PI3K inhibitor. HGF transactivated several RTKs in IEC6 cells, indicating that its effects extended to multiple signaling pathways. Finally, similar to amniotic fluid, recombinant HGF also reduced the frequency and severity of NEC-like injury in rat pups. Amniotic fluid supplementation protects rat pups against experimental NEC, which is mediated, at least in part, by HGF.

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