The effects of IGF-1 and IGFBP-2 treatments on the atherosclerosis in the aorta and the coronary arteries of the high cholesterol diet-fed rabbits.

Several studies have demonstrated suppression of aortic atherosclerosis by insulin like growth factor-1 (IGF-1) in hypercholesterolemic rabbits. Though a recent study has reported that IGF-1 exerts anti-atherogenic effects in coronary arteries, the mechanisms of IGF-1 in coronary arteries need to be further verified. Studies about insulin like growth factor binding protein-2 (IGFBP-2) in atherosclerosis are rarely. The objective of this study is to examine the effects of IGF-1 and IGFBP-2 on the atherosclerosis development in the aorta and coronary arteries of the high-cholesterol diet (HCD)-fed rabbits. New Zealand white rabbits were fed either normal chow (n = 5) or a diet containing 1.0 % cholesterol (n = 18) for 12 weeks. Cholesterol-fed rabbits were given IGF-1 or IGFBP-2 or saline intravenously (each n = 6) for 10 weeks. The results revealed that IGF-1 decreased total cholesterol (TC) and low-density lipoprotein (LDL) levels (p < 0.05), whereas IGFBP-2 did not. IGF-1 significantly attenuated atherosclerotic lesions and reduced accumulated macrophages within the coronary artery plaques, whereas IGFBP-2 deteriorated these changes. Moreover, IGF-1 reduced serum platelet-activating factor acetylhydrolase levels, C reactive protein (CRP), and inhibited the protein expression levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). IGFBP-2 elevated serum 8-hydroxy-2'-deoxyguanosine levels, CRP, and promoted the protein expression levels of TNF-α and IL-6. In conclusion, IGF-1 can substantially suppress plaque formation in coronary arteries with a marked inhibition of macrophage accumulation likely via its anti-inflammatory properties, whereas IGFBP-2 plays an opposite effect on atherosclerosis. The present study highlighted a theoretical basis for pharmacological treatment of atherosclerosis.

Circulating IGF-1 and IGFBP-2 may be biomarkers for risk stratification in patients with acute coronary syndrome: A prospective cohort study.

BACKGROUND AND AIM: The involvement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-2 (IGFBP-2) following acute coronary syndrome (ACS) is rarely studied in clinical practice. Therefore, we sought to evaluate the relationship between IGF-1 and IGFBP-2 concentrations at admission and risk stratification based on the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients with ACS. METHODS AND RESULTS: In all, 304 patients diagnosed with ACS were included in this study. Plasma IGF-1 and IGFBP-2 were measured using commercially available ELISA kits. The TIMI risk score was calculated and the study population was stratified into high (n = 65), medium (n = 138), and low (n = 101) risk groups. Levels of IGF-1 and IGFBP-2 were analyzed for their predictive ability of risk stratification based on the TIMI risk scores. Correlation analysis showed that IGF-1 levels were negatively correlated with TIMI risk levels (r = -0.144, p = 0.012), while IGFBP-2 levels were significantly and positively correlated with TIMI risk levels (r = 0.309, p < 0.001). In multivariate logistic regression analysis, IGF-1 (odds ratio [OR]: 0.995; 95% confidence interval [CI]: 0.990-1.000; p = 0.043) and IGFBP-2 (OR: 1.002; 95%CI: 1.001-1.003; p < 0.001) were independent predictors of high TIMI risk levels. In receiver operating characteristic curves, the area under the curve values for IGF-1 and IGFBP-2 in the prediction of high TIMI risk levels were 0.605 and 0.723, respectively. CONCLUSIONS: IGF-1 and IGFBP-2 levels are excellent biomarkers for risk stratification in patients with ACS, which provides further guidance for clinicians to identify patients at high risk and to lower their risk.

Clinical risk factors and outcomes of young patients with acute ST segment elevation myocardial infarction: a retrospective study.

BACKGROUND: This study aimed to analysis the clinical characteristics and prognosis of acute STEMI in patients aged ≤ 45 years. METHODS: Seven hundred and one patients with STEMI from Liaocheng People's Hospital from January 2018 to March 2021 were included in this study. Clinical characteristics, management, and outcomes (average follow-up: 11.5 months) were compared between patients aged ≤ 45 years and those aged > 45 years. RESULTS: Of the patients with STEMI who underwent primary percutaneous coronary intervention, 108 (15.4%) were aged ≤ 45 years. Compared to the older group, the younger patient group included more males, current smokers, and those with alcohol use disorder (AUD) or a family history of ischaemic heart disease (IHD). The culprit vessel in young patients was the left anterior descending (LAD) artery (60% vs. 45.9%, P = 0.031), which may have been due to smoking (odds ratio, 3.5; 95% confidence interval: 1.12-10.98, P = 0.042). Additionally, young patients presented with higher low-density lipoprotein and lower high-density lipoprotein levels than older patients; uric acid levels were also significantly higher in younger patients than that in the older group. Diabetes showed a trend toward major adverse cardiovascular events (MACE) in both groups; age and sex were both independent predictors of MACE in older patients. CONCLUSION: More patients who were smokers, had AUD, or a family history of IHD were present in the young patient group. Hyperuricaemia (but not dyslipidaemia) was a prevalent risk factor in patients aged ≤ 45 years. Diabetes should be controlled to reduce cardiovascular events in young patients.

The impact of circulating IGF-1 and IGFBP-2 on cardiovascular prognosis in patients with acute coronary syndrome.

Background: While insulin-like growth factor 1 (IGF-1) exerts a cardioprotective effect in the setting of atherosclerosis, insulin-like growth factor binding protein 2 (IGFBP-2) is involved in metabolic syndrome. Although IGF-1 and IGFBP-2 are known to be predictors for mortality in patients with heart failure, their use in clinic as prognostic biomarkers for acute coronary syndrome (ACS) requires investigation. We evaluated the relationship between IGF-1 and IGFBP-2 levels at admission and the risk of major adverse cardiovascular events (MACEs) in patients with ACS. Methods: A total of 277 ACS patients and 42 healthy controls were included in this prospective cohort study. Plasma samples were obtained and analyzed at admission. Patients were followed for MACEs after hospitalization. Results: Among patients who suffered acute myocardial infarction, plasma levels of IGF-1 and IGFBP-2 were lower and higher, respectively, as compared to healthy controls (both p < 0.05). The mean follow-up period was 5.22 (1.0-6.0) months and MACEs incidence was 22.4% (62 of 277 patients). Kaplan-Meier survival analysis revealed that patients with low IGFBP-2 levels had a greater event-free survival rate than patients with high IGFBP-2 levels (p < 0.001). Multivariate Cox proportional hazards analysis revealed IGFBP-2, but not IGF-1, to be a positive predictor of MACEs (hazard ratio 2.412, 95% CI 1.360-4.277; p = 0.003). Conclusion: Our findings suggest that high IGFBP-2 levels are associated with the development of MACEs following ACS. Moreover, IGFBP-2 is likely an independent predictive marker of clinical outcomes in ACS.

NLRP3 Inflammasome May Be a Biomarker for Risk Stratification in Patients with Acute Coronary Syndrome.

Purpose: Acute coronary syndrome (ACS) has a high incidence and mortality rate worldwide, which has a considerable negative impact on the global economy. This study aimed to identify a group of ACS patients at a high risk of recurrent adverse cardiac events using the plasma NLRP3 inflammasome. Patients and methods: ACS patients admitted to Liaocheng People's Hospital between June 2021 and March 2022 were enrolled in this study. Patients were divided into low (levels < 3.84 ng/mL) and high (levels ≥ 3.84 ng/mL) groups based on the median NLRP3 inflammasome levels. The patients were divided into three groups according to the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P): low (scores ≤ 2 points), intermediate (scores = 3 points), and high (score ≥ 4 points) risk. We investigated the relationship between NLRP3 inflammasome and laboratory indicators. Additionally, we examined whether the NLRP3 inflammasome was an independent predictor of high TRS-2P and explored the applicability of the plasma NLRP3 inflammasome for predicting high TRS-2P. Results: Logistic regression analysis revealed that NLRP3 inflammasome was an independent predictor of high TRS-2P (odds ratio [OR]:2.013; 95% confidence interval [CI]: 1.174-3.452). The area under the receiver operating characteristic curve value of the NLRP3 inflammasome was 0.674 (95% CI: 0.611-0.737; P < 0.001). Conclusion: NLRP3 inflammasome levels are an independent predictive factor for high TRS-2P levels, which indicates that the NLRP3 inflammasome may help predict the prognosis of ACS patients.

Gender-Related Difference in D-Dimer Level Predicts In-Hospital Heart Failure after Primary PCI for ST-Segment Elevation Myocardial Infarction.

AIMS: The prognostic value of plasma D-dimer in patients with coronary artery disease (CAD) remains controversial. The study is aimed at investigating the relationship between plasma D-dimer levels and in-hospital heart failure (HF) in ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI). METHODS: STEMI patients who underwent pPCI were enrolled in this study. Venous blood samples were collected from patients on admission before pPCI procedure. The study endpoint was the occurrence of in-hospital HF. The participants were divided into two groups according to plasma D-dimer levels and further compared baseline D-dimer levels between male and female. Logistic regression and receiver operating characteristic (ROC) curves were performed to evaluate the relationship of D-dimer and in-hospital HF. RESULTS: A total of 778 patients were recruited in the study, of which 539 (69.3%) patients had normal D-dimer levels (≤0.5 mg/L) while 239 (30.7%) had increased D-dimer levels (>0.5 mg/L). The female patients have higher D-dimer levels and higher incident rate of in-hospital HF than that in male patients (p < 0.001). The multivariate logistic regression model revealed that D-dimer was an independent predictor for in-hospital HF in overall population (adjusted odds ratio [OR]: 1.197, 95% CI: 1.003-1.429, and p = 0.046) and female patients (adjusted OR: 1.429, 95% CI: 1.083-1.885, and p = 0.012). CONCLUSION: Increased plasma D-dimer levels were an independent risk factor for incidence of in-hospital HF in STEMI patients who underwent pPCI, especially in female patients, which provides guidance for clinicians in identifying patients at high risk of developing HF and lowering their risk.

Leukocyte telomere length: a potential biomarker for the prognosis of coronary artery disease.

Aim: This study aimed to explore the prognostic value of leukocyte telomere length (LTL) in patients with coronary artery disease (CAD). Materials & methods: We enrolled 366 CAD patients and 76 healthy subjects in this study. LTL was measured. All subjects were followed up for 6 months for further analysis regarding major adverse cardiac events (MACEs). Results: CAD patients had a significantly shortened LTL compared with healthy subjects (p < 0.05). The area under the curve for LTL prediction of MACEs was 0.769 (p < 0.001), with a shorter LTL being an independent predictor of MACEs (Cox proportional hazards regression, hazard ratio: 2.866; p < 0.001). Conclusion: LTL could be considered as an independent predictor of short-term MACEs in CAD.

Predictive value of leukocyte telomere length for the severity of coronary artery disease.

Aim: This study aimed to explore leukocyte telomere length (LTL) in the prediction of the severity of coronary artery disease (CAD). Materials & methods: A total of 359 CAD patients who underwent coronary angiography were enrolled in this study. Severity of coronary artery was assessed by Gensini score (GS). Results: LTL is negatively correlated with GS (Spearman's rank correlation coefficient = -0.335; p < 0.001). Multivariate logistic regression results showed that LTL was an independent predictor of high GS (p = 0.001). Area under the curve value of LTL for predicting high GS was 0.659 (p < 0.001). Conclusion: LTL could be considered as a potential predictor of the severity of coronary artery in patients with CAD.

Diagnostic and prognostic impact of circulating microRNA-208b and microRNA-499 in patients with acute coronary syndrome.

Aim: This study aimed to investigate the correlation between the expression of circulating miR-208b and miR-499 and acute coronary syndrome (ACS) patients. Materials & methods: A total of 160 consecutive patients with ACS and 48 healthy control subjects were enrolled for primary analysis. The ACS patients (n = 160) were followed up for 6 months for further analysis regarding major adverse cardiac events. Results: Area under the curve values of miR-208b and miR-499 for predicting ACS were 0.910 and 0.851 (p < 0.001, respectively). Cox proportional hazards regression analysis revealed that miR-208b but not miR-499 was an independent predictor of major adverse cardiac events. Conclusion: Circulating miR-208b and miR-499 could be considered as diagnostic or prognostic biomarkers for patients with ACS.

Plasma miR-208b and miR-499: Potential Biomarkers for Severity of Coronary Artery Disease.

AIMS: MicroRNAs (miRNAs) are associated with the pathogenesis of coronary artery disease (CAD). The objective of this study is to explore plasma levels of miR-208b and miR-499 in CAD and analyze its association with the severity of CAD. MATERIALS AND METHODS: 195 consecutive CAD patients who underwent coronary angiography were enrolled in this study. Severity of coronary lesions was evaluated by the synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX) score (SS). Plasma levels of miR-208b and miR-499 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-208b and miR-499 and SS was analyzed. RESULTS: The qRT-PCR results showed that plasma levels of miR-208b and miR-499 in SS > 32 (high SS) group was higher than those in low (SS ≤ 22) and intermediate (22 < SS ≤ 32) groups. Meanwhile, plasma miR-208b and miR-499 levels were significantly positive correlated with the SS (Spearman's r = 0.535 and r = 0.407, respectively; both p < 0.001). Multivariate logistic analysis results showed that miR-208b (odds ratio [OR]: 2.069; 95% confidence interval [CI]: 1.351-3.167; p = 0.001) and miR-499 (OR: 1.652; 95% CI: 1.222-2.233; p = 0.001) were independent predictors of high SS. In receiver operating characteristic curve, the area under the curve of miR-208b and miR-499 in prediction of high SS was 0.775 and 0.713, respectively. CONCLUSIONS: Higher plasma levels of miR-208b and miR-499 were positively associated with the severity of CAD, and plasma miR-208b and miR-499 can act as potential biomarkers for estimating the severity of CAD.

High sensitivity C-reactive protein to prealbumin ratio measurement as a marker of the prognosis in acute coronary syndrome.

The study aimed to determine whether high sensitivity C-reactive protein to prealbumin (hs-CRP/PAB) ratio could be used to predict in-hospital major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). A total of 659 patients with ACS were included in the study. Patients were divided into two groups: high hs-CRP/PAB ratio group (hs-CRP/PAB ≥0.010) and low hs-CRP/PAB ratio group (hs-CRP/PAB <0.010). MACE was defined as death, cardiogenic shock, re-infarction and acute heart failure. Logistic regression was performed and the receiver operating characteristic curve (ROC) was generated to evaluate the correlation of hs-CRP/PAB ratio and MACE in patients with ACS. The occurrence rate of MACE was significantly higher in high hs-CRP/PAB ratio group when compared with that in low hs-CRP/PAB ratio group (P < 0.001). Multivariable analysis determined that hs-CRP/PAB ratio was an independent predictor of MACE (adjusted odds ratio: 1.276, 95% confidence interval: 1.106-1.471, P = 0.001). Moreover, the area under the curve value of hs-CRP/PAB ratio for predicting MACE was higher than hs-CRP and equal to PAB. High hs-CRP/PAB ratio was considered as a prognostic parameter of MACE in ACS patients, with the predictive power equal to PAB but greater than hs-CRP.

Prognostic efficacy of high-sensitivity C-reactive protein to albumin ratio in patients with acute coronary syndrome.

Aim: The present study aimed to examine the correlation between high-sensitivity CRP to albumin ratio (CAR) and in-hospital and short-term major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). Materials & methods: We analyzed 652 consecutive patients who had been hospitalized for ACS. The MACEs were defined as cardiogenic shock, reinfarction, acute heart failure and all-cause death. Results: The incidence rate of MACEs was significantly higher in the high CAR (≥0.114) group than in the low CAR (<0.114) group. Multivariate analysis revealed that CAR, hs-CRP and albumin were independent predictors for increased risk for MACEs. Conclusion: The CAR was independently correlated with in-hospital and short-term MACEs and can be used for risk stratification in patients with ACS.

HMGB1 Protects the Heart Against Ischemia-Reperfusion Injury via PI3K/AkT Pathway-Mediated Upregulation of VEGF Expression.

Delivery of exogenous high mobility group box 1 (HMGB1) may exert a beneficial effect on myocardial ischemia-reperfusion (I/R) injury. Since the expression of vascular endothelial growth factor (VEGF) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in the myocardium mediates the cardioprotective function of basic fibroblast growth factor, we hypothesized that VEGF and the PI3K/Akt signaling pathway also mediate the protective effects of intravenously delivered HMGB1. Thus, the objective of the present study was to analyze the impact of intravenous administration of HMGB1 on the myocardial expression of VEGF, myocardial fibrosis, and cardiac function in rats subjected to acute myocardial I/R. The ischemia was induced by ligation of the left anterior descending coronary artery for 30 min and was followed by 3 h of reperfusion. Myocardial malondialdehyde content, infarct size, and collagen volume fraction decreased, while the activity of superoxide dismutase was increased, the expression of VEGF and p-Akt was upregulated, and cardiac function was improved in the HMGB1-treated group when compared with rats subjected to I/R only (all P < 0.05). However, these effects of HMGB1 were abolished by LY294002. The obtained results demonstrate that the cardioprotective effects of intravenous administration of HMGB1 prior to I/R may be mediated by upregulation of myocardial expression of VEGF, which may activate the PI3K/Akt signaling pathway.

Low serum prealbumin levels on admission can independently predict in-hospital adverse cardiac events in patients with acute coronary syndrome.

The aim of this study is to evaluate if low prealbumin levels on admission predict subsequent adverse cardiac events in patients hospitalized with acute coronary syndrome (ACS).We designed a cohort study and enrolled 610 consecutive patients with ACS from whom venous blood for serum prealbumin measurement was drawn immediately upon hospital admission. Patients were classified in two groups according to prealbumin level: "normal" prealbumin levels (≥17 mg/dL, n=413) and "low" prealbumin (<17 mg/dL, n = 197). In-hospital adverse cardiac events were death, acute heart failure, reinfarction, and cardiogenic shock. Univariate and multivariable analyses were applied to evaluate the prediction value of low prealbumin.The incidence of in hospital adverse cardiac events is 10.8%. The proportion of adverse cardiac events was significantly higher in low prealbumin group as compared with normal prealbumin group (20.8% versus 6.1%, P < .001). Univariate analysis indicates that low prealbumin levels can predict in hospital adverse cardiac events (odds ratio [OR]: 0.834, 95% confidence interval [CI]: 0.785-0.886, P < .001). Multivariable analysis shows that low prealbumin level was an independent predictor for in hospital adverse cardiac events (adjusted OR: 0.918, 95% CI: 0.848-0.993, P = .033). Other independent predictors were lower in average hemoglobin level and Killip class II-IV on admission.Therefore, lower serum prealbumin levels on admission can independently predicts subsequent in hospital major adverse cardiac events in patients with ACS.

HGF Reduces Disease Severity and Inflammation by Attenuating the NF-κB Signaling in a Rat Model of Pulmonary Artery Hypertension.

The purpose of the present study was to investigate the anti-inflammatory effect of hepatocyte growth factor (HGF) on pulmonary artery hypertension (PAH) in a rat model and underlying mechanisms. Wistar rats were treated with monocrotaline intravenously to induce PAH and then treated with vehicle or HGF for 2 weeks, respectively. The mean pulmonary artery pressure (mPAP), the index of right heart ventricular hypertrophy (RHVI), pathological changes, and inflammation in the lungs of individual rats were measured. The levels of serum inflammatory interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and high mobility group protein B1 (HMGB1) and the relative levels of IκBα and NF-κB p65 expression in the lungs of individual rats were determined by methods of enzyme-linked immunosorbent assay (ELISA) and Western blot. The levels of mPAP and RVHI in the HGF group were significantly lower than that in the PAH group (P < 0.05), but remained significantly higher than that of the control group (P < 0.05). Similar patterns of inflammatory scores and the levels of serum IL-6, TNF-α, ICAM-1, and HMGB1 were detected among the different groups of rats. Furthermore, the relative levels of IκBα expression in the lungs of the HGF group of rats were significantly higher than that in the control group, which were significantly higher than that in the PAH group. In contrast, the relative levels of NF-kB p65 expression in the HGF group were significantly lower than that in the PAH group (P < 0.05). HGF treatment significantly mitigated the severity of PAH and inhibited inflammation by attenuating the NF-kB signaling in the lungs of PAH rats.

High mobility group box 1 protein attenuates myocardial ischemia reperfusion injury via inhibition of the p38 mitogen-activated protein kinase signaling pathway.

The present study aimed to determine the effects of high mobility group box 1 protein (HMGB1) on myocardial ischemia reperfusion (I/R) injury in rats following acute myocardial ischemia and investigate the underlying molecular mechanisms of these effects. Male Wistar rats were randomly divided into the following groups (n=10/group): Sham operation; I/R; HMGB50 (50 ng/kg HMGB1 before I/R); HMGB100 (100 ng/kg HMGB1 before I/R); and HMGB200 (200 ng/kg HMGB1 before I/R). Serum cardiac troponin I (cTnI), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were subsequently measured. Myocardial levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were also determined. Myocardial infarction size (IS) was determined by 2,3,5-triphenyltetrazolium chloride staining. Myocardial expression of hypoxia inducible factor (HIF)-1α and phosphorylated p38 mitogen-activated protein kinase (P-p38 MAPK) protein was measured using western blotting. The results demonstrated that HMGB1 significantly decreased serum levels of cTnI, IL-6 and TNF-α and myocardial IS in I/R rats compared with the sham group (all P<0.05). HMGB1 also significantly decreased and increased myocardial levels of MDA and SOD, respectively (both P<0.05). HMGB1 significantly increased myocardial expression of HIF-1α and decreased expression of P-p38 MAPK following I/R (both P<0.05). These effects of HMGB1 occurred in a dose-dependent manner. The results of the current study indicate that the cardioprotective effects of intravenous HMGB1 are associated with increased myocardial expression of HIF-1α via inhibition of P-p38 MAPK expression, leading to inhibition of the P-p38 MAPK signaling pathway.