Association between admission blood pressure and spontaneous reperfusion and long-term prognosis in STEMI patients: an observational and multicenter study.

BACKGROUND: This study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients. METHODS: Data from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2-3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics. RESULTS: Admission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95% CI: 0.706-0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958-1.084, p = 0.552). In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality compared with those SBP ≤ 120mmHg (adjusted HR: 0.653; 95% CI: 0.495-0.862; p = 0.003). In addition, subgroups analysis with Killip class I-II showed SBP ≤ 120mmHg was still associated with increased risk of mortality. CONCLUSION: The present study revealed admission SBP above 120 mmHg was associated with higher SR,30-d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04996901), 07/27/2021.

Downregulation of P300/CBP-Associated Factor Protects from Vascular Aging via Nrf2 Signal Pathway Activation.

Increasing evidence has shown that vascular aging has a key role in the pathogenesis of vascular diseases. P300/CBP-associated factor (PCAF) is involved in many vascular pathological processes, but the role of PCAF in vascular aging is unknown. This study aims to explore the role and underlying mechanism of PCAF in vascular aging. The results demonstrated that the expression of PCAF was associated with age and aging, and remarkably increased expression of PCAF was present in human atherosclerotic coronary artery. Downregulation of PCAF could reduce angiotensin II (AngII)-induced senescence of rat aortic endothelial cells (ECs) in vitro. In addition, inhibition of PCAF with garcinol alleviated AngII-induced vascular senescence phenotype in mice. Downregulation of PCAF could alleviate AngII-induced oxidative stress injury in ECs and vascular tissue. Moreover, PCAF and nuclear factor erythroid-2-related factor 2 (Nrf2) could interact directly, and downregulation of PCAF alleviated vascular aging by promoting the activation of Nrf2 and enhancing the expression of its downstream anti-aging factors. The silencing of Nrf2 with small interfering RNA attenuated the protective effect of PCAF downregulation from vascular aging. These findings indicate that downregulation of PCAF alleviates oxidative stress by activating the Nrf2 signaling pathway and ultimately inhibits vascular aging. Thus, PCAF may be a promising target for aging-related cardiovascular disease.

Assessing myocardial infarction severity from the urban environment perspective in Wuhan, China.

Health inequalities are globally widespread due to the regional socioeconomic inequalities. Myocardial infarction (MI) is a leading health problem causing deaths worldwide. Yet medical services for it are often inequitably distributed by region. Moreover, studies concerning MI's potential spatial risk factors generally suffer from difficulties in focusing on too few factors, inappropriate models, and coarse spatial grain of data. To address these issues, this paper integrates registered 1098 MI cases and urban multi-source spatio-temporal big data, and spatially analyses the risk factors for MI severity by applying an advanced interpretable model, the random forest algorithm (RFA)-based SHapley Additive exPlanations (SHAP) model. In addition, a community-scale model between spatio-temporal risk factors and MI cases is constructed to predict the MI severity of all communities in Wuhan, China. The results suggest that those risk factors (i.e., age of patients, medical quality, temperature changes, air pollution and urban habitat) affect the MI severity at the community scale. We found that Wuhan residents in the downtown area are at risk for high MI severity, and the surrounding suburb areas show a donut-shape pattern of risk for medium-to-high MI severity. These patterns draw our attention to the impact of spatial environmental risk factors on MI severity. Thus, this paper provides three recommendations for urban planning to reduce the risk and mortality from severe MI in the aspect of policy implication.

Downregulation of p300/CBP-associated factor inhibits cardiomyocyte apoptosis via suppression of NF-κB pathway in ischaemia/reperfusion injury rats.

Cardiomyocyte apoptosis is the main reason of cardiac injury after myocardial ischaemia-reperfusion (I/R) injury (MIRI), but the role of p300/CBP-associated factor (PCAF) on myocardial apoptosis in MIRI is unknown. The aim of this study was to investigate the main mechanism of PCAF modulating cardiomyocyte apoptosis in MIRI. The MIRI model was constructed by ligation of the rat left anterior descending coronary vessel for 30 min and reperfusion for 24 h in vivo. H9c2 cells were harvested after induced by hypoxia for 6 h and then reoxygenation for 24 h (H/R) in vitro. The RNA interference PCAF expression adenovirus was transfected into rat myocardium and H9c2 cells. The area of myocardial infarction, cardiac function, myocardial injury marker levels, apoptosis, inflammation and oxidative stress were detected respectively. Both I/R and H/R remarkably upregulated the expression of PCAF, and downregulation of PCAF significantly attenuated myocardial apoptosis, inflammation and oxidative stress caused by I/R and H/R. In addition, downregulation of PCAF inhibited the activation of NF-κB signalling pathway in cardiomyocytes undergoing H/R. Pretreatment of lipopolysaccharide, a NF-κB pathway activator, could blunt these protective effects of PCAF downregulation on myocardial apoptosis in MIRI. These results highlight that downregulation of PCAF could reduce cardiomyocyte apoptosis by inhibiting the NF-κB pathway, thereby providing protection for MIRI. Therefore, PCAF might be a promising target for protecting against cardiac dysfunction induced by MIRI.

Development and validation of a risk prediction nomogram for in-stent restenosis in patients undergoing percutaneous coronary intervention.

BACKGROUND: This study aimed to develop and validate a nomogram to predict probability of in-stent restenosis (ISR) in patients undergoing percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI with drug-eluting stents between July 2009 and August 2011 were retrieved from a cohort study in a high-volume PCI center, and further randomly assigned to training and validation sets. The least absolute shrinkage and selection operator (LASSO) regression model was used to screen out significant features for construction of nomogram. Multivariable logistic regression analysis was applied to build a nomogram-based predicting model incorporating the variables selected in the LASSO regression model. The area under the curve (AUC) of the receiver operating characteristics (ROC), calibration plot and decision curve analysis (DCA) were performed to estimate the discrimination, calibration and utility of the nomogram model respectively. RESULTS: A total of 463 patients with DES implantation were enrolled and randomized in the development and validation sets. The predication nomogram was constructed with five risk factors including prior PCI, hyperglycemia, stents in left anterior descending artery (LAD), stent type, and absence of clopidogrel, which proved reliable for quantifying risks of ISR for patients with stent implantation. The AUC of development and validation set were 0.706 and 0.662, respectively, indicating that the prediction model displayed moderate discrimination capacity to predict restenosis. The high quality of calibration plots in both datasets demonstrated strong concordance performance of the nomogram model. Moreover, DCA showed that the nomogram was clinically useful when intervention was decided at the possibility threshold of 9%, indicating good utility for clinical decision-making. CONCLUSIONS: The individualized prediction nomogram incorporating 5 commonly clinical and angiographic characteristics for patients undergoing PCI can be conveniently used to facilitate early identification and improved screening of patients at higher risk of ISR.

Down-regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats.

Patients with diabetes have an increased risk of vascular complications. Suv39h1, a histone methyltransferase, plays a protective role against myocardial injury in diabetes. Herein, we intend to explore whether Suv39h1 could affect neointimal formation after vascular injury in diabetic rats and reveal the underlying mechanism. In this study, we generated adenovirus expressing Suv39h1 as well as lentivirus expressing Suv39h1-targeting shRNA and evaluated the significance of Suv39h1 in vascular smooth muscle cells (VSMCs) under diabetic conditions. In vitro, we examined proliferative and migratory behaviours as well as the underlying signalling mechanisms in VSMCs in response to high glucose treatment. In vivo, we induced diabetes in SD rats with streptozocin and established the common carotid artery balloon injury model. Suv39h1 was found to be both necessary and sufficient to promote VSMC proliferation and migration under high glucose conditions. We observed corresponding changes in intracellular signalling molecules including complement C3 and phosphor-ERK1/2. However, either up-regulating or down-regulating Suv39h1, phosphor-p38 level was not significantly affected. Consistently, Suv39h1 overexpression led to accelerated neointima formation, while knocking down Suv39h1 reduced it following carotid artery injury in diabetic rats. Using microarray analyses, we showed that altering the Suv39h1 level in vivo dramatically altered the expression of myriad genes mediating different biological processes and molecular function. This study reveals the novel role of Suv39h1 in VSMCs of diabetes and suggests its potential role as a therapeutic target in diabetic vascular injury.

In-Hospital Management and Outcomes of Acute Myocardial Infarction Before and During the Coronavirus Disease 2019 Pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. This study sought to share our experiences with in-hospital management and outcomes of acute myocardial infarction (AMI) during the COVID-19 pandemic. We retrospectively analyzed consecutive AMI patients, including those with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), from February 1, 2020, to April 15, 2020 (during the COVID-19 pandemic), and from January 1, 2019, to December 31, 2019 (before the COVID-19 pandemic), respectively. Fifty-three AMI patients (31 STEMI, 22 NSTEMI) during the COVID-19 pandemic were matched to 53 AMI patients before the pandemic. Baseline characteristics were comparable between the matched patients. STEMI patients during the COVID-19 pandemic had a longer delay time, less primary or remedial PCI and more emergency thrombolysis than those before the pandemic. Less coronary angiography and stenting were performed in AMI patients during the COVID-19 pandemic than before the pandemic. There were no statistically significant differences in the clinical outcomes between the matched patients. However, STEMI patients during the COVID-19 pandemic had a 4-fold (12.9% vs. 3.2%) increase in all-cause mortality rate compared with those before the pandemic. AMI combined with COVID-19 infection was associated with higher rates of mortality than AMI alone. This study demonstrates that the COVID-19 pandemic results in significant reperfusion delays in STEMI patients and has a marked impact on the treatment options selection in AMI patients. The mortality rate of STEMI patients exhibits an increasing trend during the pandemic of COVID-19.

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy.

Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. This study was to investigate whether downregulation of PCAF attenuate MIRI. The results showed that the expression of PCAF was significantly increased in MIRI in vivo and in vitro. Downregulation of PCAF not only inhibited autophagy and damage of H9c2 cells induced by hypoxia-reoxygenation, but also reduced autophagy and myocardial infarct size during myocardial ischemia-reperfusion in rats. In addition, downregulation of PCAF promoted activation of PI3K/Akt/mTOR signaling pathway in cardiomyocytes during hypoxia-reoxygenation. Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.

Downregulation of the transcriptional co-activator PCAF inhibits the proliferation and migration of vascular smooth muscle cells and attenuates NF-κB-mediated inflammatory responses.

P300/CBP-associated factor (PCAF) regulates vascular inflammation. This study was to explore the effect of PCAF on the proliferation and migrationof vascular smooth muscle cells (VSMCs) and neointimal hyperplasia in balloon-injured rat carotid artery. Downregulation of PCAF remarkably suppressed VSMCs proliferation and migration induced by lipopolysaccharide, and also significantly inhibit the nuclear translocation of nuclear factor-kappaB p65. Meanwhile, downregulation of PCAF inhibited the mRNA expression of tumor necrosis factor-α and interleukin-6, and also the levels in culture supernatants. Moreover, downregulation of PCAF profoundly reduced the intima area and the ratio of intima area to media area in balloon-injured rat carotid artery. In addition, the expression of PCNA and NF-κB p65 in intima were decreased by downregulation of PCAF. These results highlight that PCAF may be a potential target for prevention and treatment of neointimal hyperplasia and restenosis after angioplasty.

Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the chronic inflammation regulated by various inflammatory factors are the major pathological processes in the development of neointimal hyperplasia and in-stent restenosis after angioplasty. Cantharidin is a potent and selective inhibitor of protein phosphatase 2A, which plays pivotal roles in cell cycle progression, cell fate, and inflammation. This study was to explore whether Cantharidin could inhibit VSMCs proliferation, migration and inflammation. Transwell migration assay, Cell Counting Kit 8 and flow cytometry were performed. Western blot, Quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of the markers. Results showed that Cantharidin remarkably suppressed VSMCs proliferation and migration induced by platelet derived growth factor (PDGF)-BB. Meanwhile, Cantharidin could significantly inhibit the phosphorylation of Akt (P-AKT) and p38 mitogen-activated protein kinase (MAPK) (P-p38), the expression of p38 MAPK (p38), and also the phosphorylation level of nuclear factor-kappaB (NF-κB) p65 (p65). Cantharidin obviously inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and also the level of IL-6 and TNF-α in culture supernatants. Inhibitors for p38 MAPK, phosphatidylinositol 3-kinase (PI3K) /AKT and NF-κB signaling pathways did not affect the inhibition of Cantharidin on VSMCs proliferation, migration and inflammation. These findings indicated that Cantharidin could significantly inhibit the proliferation, migration and inflammatory response of VSMCs, which suggested that Cantharidin may be a potential inhibitor for neointimal hyperplasia and restenosis after angioplasty.

Downregulation of microRNA-17-5p improves cardiac function after myocardial infarction via attenuation of apoptosis in endothelial cells.

MicroRNA-17-5p (miR-17-5p) was indicated to suppress the formation of blood vessels, which is associated with cardiac function after myocardial infarction. In this study, the relationship between miR-17-5p and cardiac function was researched. Human umbilical vein endothelial cells were infected with adenoviruses. Apoptosis was determined by Annexin V-7AAD/PI. Real-time RT-PCR was used to evaluate miR-17-5p and ERK levels. Western blotting was used to determine the levels of ERK, the anti-apoptosis protein bcl-2 and apoptosis proteins, including bax, caspase 3, and caspase 9. An in vivo acute myocardial infarction (AMI) model was established in SD male rats. Heart function was evaluated by echocardiography prior to inducing AMI and after 7 and 28 days later. The heart was removed to perform histological examination, real-time RT-PCR, and western blotting, as described above. The result indicated that the ERK pathway was activated by miR-17-5p downregulation and an increase in the level of the anti-apoptosis protein bcl-2; however, the levels of apoptosis proteins (bax/caspase 3/caspase 9) were decreased. The results were completely reversed when miR-17-5p was up-regulated. At 7 and 28 days after the induction of AMI, in the miR-17-5p inhibition group, the infarction areas and collagen fibers were decreased, apoptosis in cardiac tissues was inhibited, and the endothelial growth process was promoted. Therefore, MiR-17-5p silencing protects heart function after AMI through decreasing the rate of apoptosis and repairing vascular injury.

Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence via the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells.

Endothelial senescence has been proposed to be involved in endothelial dysfunction and atherogenesis. Curcumin, a natural phenol, possesses antioxidant and anti-inflammatory properties. However, the effect of curcumin on endothelial senescence is unclear. This study explores the effect of curcumin on hydrogen peroxide (H2O2)-induced endothelial premature senescence and the mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured, and premature senescence was induced with 100 µM H2O2. Results showed that pretreatment with curcumin significantly attenuated the H2O2-induced HUVECs' premature senescence, which was evidenced by a decreased percentage of senescence-associated ß-galactosidase positive cells, improved cell division and decreased expression of senescence-associated protein p21 (all p<0.05). Pretreatment with curcumin decreased oxidative stress and apoptosis in H2O2-treated HUVECs. Treatment of HUVECs with H2O2 also down-regulated the phosphorylation of endothelial nitric oxide synthase (eNOS), decreased the level of nitric oxide in the culture medium, and inhibited the protein expression and enzymatic activity of silent information regulator 1 (SIRT1), while pretreatment with curcumin partly reversed these effects (all p<0.05). Treatment with curcumin alone enhanced the enzymatic activity of SIRT1, but didn't affect cellular senescence, cell growth or apoptosis compared to the Control. The inhibition of SIRT1 using SIRT1 short interfering RNA (siRNA) could decrease the expression and phosphorylation of eNOS and abrogate the protective effect of curcumin on H2O2-induced premature senescence. These findings suggest that curcumin could attenuate oxidative stress-induced HUVECs' premature senescence via the activation of SIRT1.

Resveratrol inhibits phenotypic switching of neointimal vascular smooth muscle cells after balloon injury through blockade of Notch pathway.

BACKGROUND: Phenotypic switching of vascular smooth muscle cells (VSMCs) plays an initial role in neointimal hyperplasia, the main cause of many occlusive vascular diseases. The aim of this study was to measure the effects of resveratrol (RSV) on the phenotypic transformation of VSMCs and to investigate its mechanism of action. METHODS: Cultured VSMCs isolated from rat thoracic aorta were prepared with serum starvation for 72 hours followed by RSV treatment (50-200 µmol/L) and 10% serum stimulation. Male Sprague-Dawley rats, subjected to carotid arteries injury from a balloon catheter, were exposed to intraperitoneal injection of RSV (1 mg/kg) or saline and were killed after 7 or 28 days. RESULTS: Compared with cells in the serum-induced group, VSMCs in the RSV or N-[N-(3, 5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) treatment group exhibited significant decreases of proliferation and migration. The total and cytoplasmic Notch-1 levels were declined by RSV, accompanied by a significant increase in smooth muscle α-actin and smooth muscle myosin heavy chain protein. The expression of Notch-1, Jagged-1, Hey-1, and Hey-2 mRNA in balloon-injured arteries at 7 days was decreased by RSV treatment. Arteries from RSV-treated rats showed less neointimal hyperplasia, lower collagen content, and a lower rate of cells positive for proliferating cell nuclear antigen 28 days after injury, compared with saline controls. CONCLUSIONS: The results indicate that RSV can attenuate phenotypic switching of VSMCs after arterial injury through inhibition of the Notch pathway.

Inhibition of Sema4D attenuates pressure overload-induced pathological myocardial hypertrophy via the MAPK/NF-κB/NLRP3 pathways.

Sema4D (CD100) is closely related to pathological and physiological processes, including tumor growth, angiogenesis and cardiac development. Nevertheless, the role and mechanism of Sema4D in cardiac hypertrophy are still unclear to date. To assess the impact of Sema4D on pathological cardiac hypertrophy, TAC surgery was performed on C57BL/6 mice which were transfected with AAV9-mSema4D-shRNA or AAV9-mSema4D adeno-associated virus by tail vein injection. Our results indicated that Sema4D knockdown mitigated cardiac hypertrophy, fibrosis and dysfunction when exposed to pressure overload, and Sema4D downregulation markedly inhibited cardiomyocyte hypertrophy induced by angiotensin II. Meanwhile, Sema4D overexpression had the opposite effect in vitro and in vivo. Furthermore, analysis of signaling pathways showed that Sema4D activated the MAPK pathway during cardiac hypertrophy induced by pressure overload, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed Sema4D overexpression-induced deteriorated phenotype, resulting in improved cardiac function. Further research indicated that myocardial hypertrophy induced by Sema4D was closely related to the expression of the pyroptosis-related proteins PP65, NLRP3, caspase-1, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, our study demonstrated that Sema4D regulated the process of pathological myocardial hypertrophy through modulating MAPK/NF-κB/NLRP3 pathway, and Sema4D may be the promising interventional target of cardiac hypertrophy and heart failure.

Improving life's essential 8 mitigates myocardial infarction risk attributed to abnormal birth weight in later life.

Background: To prospectively assess the individual and joint effects of birth weight and the life's essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life. Methods: In 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids. Results: Low birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02-1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71-11.15), P < 0.001). Participants with low birth weight and low CVH (vs. participants with normal birth weight and high CVH) had HR of 5.97 (2.94-12.14) for MI incidence. The relative excess risk due to interaction of low birth weight and low CVH on MI was -4.11 (-8.12, -0.11), indicating a negative interaction on an additive scale. A consistent decreasing trend of MI risk along with increased LE8 score was observed across all three birth weight groups. Conclusion: Low birth weight was associated with increased MI risk, emphasizing the importance of the prenatal factor in risk prediction and prevention of MI. Improving LE8 can mitigate MI risk attributed to low birth weight.

Resveratrol attenuates oxidative stress induced by balloon injury in the rat carotid artery through actions on the ERK1/2 and NF-kappa B pathway.

BACKGROUND/AIM: Oxidative stress plays a critical role in pathogenesis of the neointimal arterial hyperplasia. The aim of the study was to evaluate effects of resveratrol (RSV) on the vascular hyperplasia stimulated by oxidative damage. METHODS: Balloon vascular injury was induced in rats that were intraperitonealy exposed to resveratrol (1 mg/kg) on 7 or 14 days after surgical procedure. Animals were euthanized on 7 or 14 days after operation. The blood level of 8-iso-prostaglandin F2α, arterial morphology as well as expression of monocyte chemotactic protein-1 and interleukin-6 in carotid wall were measured. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta. Cellular proliferation and migration assays, reactive oxygen species (ROS), superoxide dismutase (SOD) and NADPH oxidative activity, protein level of ß-actin, histone H3, NF-ĸB p65, IĸB, ERK1/2, phospho-ERK1/2, phospho-p38 as well as NF-ĸB transcription activity were evaluated in-vitro after angiotensin II stimulation and resveratrol (50-200 µmol/L) treatment. RESULTS: Significant decreases in neointimal/medial area, serum prostaglandin level and genes expression were found in rats treated with resveratrol, when compared to the control group. Significant changes were also revealed for proliferation and migration rates, ROS level, as well as SOD, NADPH oxidase, ERK1/2 phosphorylation and NF-ĸB transcriptional activity in cell cultures exposed to highest dose of resveratrol. Insignificant changes were observed for NF-kappaB p65 translocation and IĸB degradation, p38 phosphorylation in MAPK pathway. CONCLUSION: Resveratrol significantly suppressed the neointimal hyperplasia after balloon injury through inhibition of oxidative stress and inflammation by blocking the ERK1/2/NF-kappa B pathway.

Naringenin inhibits angiotensin II-induced vascular smooth muscle cells proliferation and migration and decreases neointimal hyperplasia in balloon injured rat carotid arteries through suppressing oxidative stress.

Proliferation and migration of vascular smooth muscle cells (VSMCs) play pivotal roles in the development of restenosis after angioplasty and oxidative stress involves both processes. Naringenin, a flavanone compound found in citrus fruits, has been widely evaluated for antioxidant activity. This study was designed to explore whether naringenin could inhibit angiotensin II-induced VSMCs proliferation and migration and decrease neointimal hyperplasia in balloon injured rat carotid arteries. VSMCs were treated with or without naringenin before stimulation with 1 µM angiotensin II and twenty-four rats were subjected to carotid arteries injury and the carotid arteries were harvested at 14 d after balloon injury. The results showed naringenin led to a significant inhibition of angiotensin II-induced VSMCs proliferation and migration. Naringenin significantly attenuated the reactive oxygen species production, increased the superoxide dismutase activity and decreased the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reduced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) and the nuclear translocation of nuclear factor (NF)-κB p65 in angiotensin II-treated VSMCs. Moreover, naringenin decreased the ratio of neointima to media by 63.8% in balloon injured rat carotid arteries, and the serum level of 8-iso-prostaglandin F2α in naringenin-treated rats was significantly decreased. These results indicated naringenin exhibited antioxidant activity on angiotensin II-treated VSMCs and balloon injured rat carotid arteries and could be a potential protective agent for restenosis after angioplasty.

Angio-based coronary functional assessment predicts 30-day new-onset heart failure after acute myocardial infarction.

AIMS: Suboptimal perfusion leading to heart failure (HF) often occurs after ST-segment elevation myocardial infarction (STEMI), despite restoration of epicardial coronary flow in primary percutaneous coronary intervention (PPCI) era. We determined the clinical implications of angio-based coronary functional assessment in evaluation of suboptimal perfusion and further outcomes among STEMI patients after successful PPCI. METHODS AND RESULTS: In this study, STEMI patients in the Chinese STEMI PPCI registry trial (NCT04996901) who achieved post-PPCI thrombolysis in myocardial infarction grade 3 flow were retrospectively screened. Post-procedural quantitative flow ratio (QFR), angio-based microvascular resistance (AMR), and coronary flow velocity (CFV) of the infarct-related artery were calculated. QFR and AMR measure epicardial stenosis severity and microvascular resistance, respectively. QFR+ was defined as QFR < 0.90 while QFR- was QFR ≥ 0.90. AMR+ was defined as AMR ≥ 250 mmHg*s/m while AMR- was AMR < 250 mmHg*s/m. The primary outcome was 30-day new-onset HF. The Kaplan-Meier curves were used to establish the associations between QFR, AMR, CFV, and HF incidences. The relationship between CFV and combined QFR and AMR indices was further assessed. Independent predictors were determined using Cox regression analysis. The receiver-operating characteristic curve was used to assess discriminant ability to predict HF. A total of 942 patients (mean age was 57.8 ± 11.7 years and 84.6% were men) were enrolled. Among them, 129 patients had new-onset HF episodes. Patients in the QFR-/AMR- group had a low risk of HF compared with those in the QFR+/AMR+ group (10.5% vs. 27.3%, P = 0.027). A higher CFV ≥ 17.4 cm/s was associated with low HF incidences as compared with CFV < 17.4 cm/s (10.3% vs. 16.8%, P = 0.005), whereas isolated QFR or AMR did not reveal any marked differences in HF incidences (P = 0.150 and 0.079, respectively). The highest and lowest medians of CFV were observed in the QFR-/AMR- and QFR+/AMR+ groups, respectively. CFV correlated well with the QFR/AMR ratio (adjusted R2  = 1, P < 0.001) and post-PPCI CFV was found to be an independent predictor of post-STEMI HF (adjusted hazard ratio: 0.61, 95% confidence interval: 0.41-0.90, P = 0.012). The area under curve estimate of the multivariable regression model was 0.749. CONCLUSIONS: CFV is an integrated coronary physiological assessment approach that incorporates epicardial and microcirculatory contributions. Patients with post-PPCI CFV < 17.4 cm/s were strongly associated with a high risk for post-STEMI HF, even achieving thrombolysis in myocardial infarction grade 3 flow. The immediate angio-based coronary functional assessment is a feasible tool for evaluating suboptimal perfusion and risk stratification.

INTRA-AORTIC BALLOON PUMP REDUCES 30-DAY MORTALITY IN EARLY-STAGE CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION ACCORDING TO SCAI CLASSIFICATION.

ABSTRACT: Background: Cardiogenic shock complicating acute myocardial infarction (AMICS) remains a high 30-day mortality. Mechanical circulatory support devices are increasingly used in AMICS, but their effects on mortality vary partly because of shock severity. Aims: This study aimed to evaluate the association between intra-aortic balloon pump (IABP) and 30-day mortality in patients with early-stage AMICS. Methods: We retrospectively analyzed patients with ST-segment elevation myocardial infarction (STEMI) based on a multicenter clinical trial (NCT04996901). Patients were stratified by IABP use, and shock severity was classified according to the Society for Cardiovascular Angiography and Interventions (SCAI) SHOCK stages. The primary outcome was 30-day all-cause mortality. The association between IABP and 30-day mortality was evaluated across shock stages using propensity score matching, weighting, and logistic regression. Results: Five thousand three hundred forty-three patients were included, and 299 received IABP. The SCAI SHOCK stage was associated with 30-day mortality (odds ratio [OR], 20.19; 95% confidence interval [CI], 13.60-29.97; P < 0.001). In the 580 matched patients, a significant interaction between IABP and 30-day mortality at different shock stages was observed ( P = 0.005). Intra-aortic balloon pump was associated with lower 30-day mortality among patients with shock stage A/B (5.8% vs. 1.2%; OR, 0.19; 95% CI, 0.03-0.73; P = 0.034) but not stage C/D/E (29.3% vs. 38.1%; OR, 1.49; 95% CI, 0.84-2.65; P = 0.172). These results were confirmed by sensitivity analyses of the weighted cohort. Conclusions: Intra-aortic balloon pump reduced 30-day mortality in patients with early-stage AMICS. The SCAI SHOCK stage provides risk stratification for patients with STEMI and helps identify those who may respond well to IABP.

Exogenous high-mobility group box 1 protein injection improves cardiac function after myocardial infarction: involvement of Wnt signaling activation.

Exogenous high-mobility group box 1 protein (HMGB1) injection could prevent left ventricular remodeling and enhance left ventricular function during myocardial infarction (MI). However, the mechanism remains unclear. This paper was to investigate in the mechanism of cardioprotection of HMGB1 during MI in rats. Anesthetized male rats were treated once with HMGB1 (200 ng) 4 h after MI and then executed after 7 and 28 days, respectively. Cardiac function, collagen deposition, and dishevelled-1 and ß-catenin protein expression were measured. After MI 7 days or 28 days, the left ventricular ejection fraction (LVEF) was significantly decreased compared to that of sham-operated control group (P < 0.05). However, the LVEF HMGB1-treated groups were significantly higher compared to those of the MI group in both 7 days and 28 days (P < 0.05). The collagen volume fraction was significantly reduced in the HMGB1-treated group in infarcted border zone. HMGB1 could activate the expression of dishevelled-1 and ß-catenin proteins (P < 0.05). Our study suggested that exogenous high-mobility group box 1 protein injection improves cardiac function after MI, which may be involved in Wnt/ß-catenin signaling activation.