HDL signaling and protection against coronary artery atherosclerosis in mice

Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high density lipoprotein（HDL） are associated with reduced risk of atherosclerosis and preclinical,animal model studies demonstrate that this association is causative.Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics.Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall.These signaling responses require the HDL receptor,scavenger receptor class B type 1（SR-B1）,an adaptor protein（PDZK1） that binds to the cytosolic C terminus of SR-B1,Akt1 activation and（at least in endothelial cells） activation of endothelial NO synthase（eNOS）.Mouse models of atherosclerosis,exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice（apoE or LDLR KO） develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis.On the other hand,inactivation of each of the components of HDL signaling（above）in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.

ASSOCIATION OF INSULIN RESISTANCE AND C-REACTIVE PROTEIN WITH CORONARY ARTERY DISEASE IN PATIENTS WITH NORMAL GLUCOSE TOLERANCE

Objective To examine insulin resistance and high sensitivity C-reactive protein （hsCRP） association with clinical and angiographic severity of coronary artery disease （CAD） in patients with normal glucose tolerance. Methods In 638 consecutive patients with normal glucose tolerance, 221 had atypical chest pain and normal coronary artery （control group）, 279 had stable angina and CAD （SAP group ）, and 138 suffered acute myocardial infarction （ MI group）. The degree of CAD was further divided into borderline lesion （ lumen diameter narrowing 50% - 69% ）, significant 1-, 2- or 3-vessel disease （ luminal diameter narrowing 〉I 70% ）. Fasting serum glucose, insulin and hsCRP levels and lipid profiles were measured, and homeostasis model assessment for insulin resistance （ HOMA-IR ） was calculated. Multivariate analysis was performed to assess risk factors for 3-vessel disease or acute MI. Results Serum hsCRP, lipoprotein （a） levels, and insulin resistance index （IRI） were higher in AMI group than those in SAP and control groups. Serum hsCRP level and IRI were also higher in 3-vessel disease than those in other groups. Multivariate regression analysis revealed that insulin resistance, cigarette smoking, serum hsCRP, and lipoprotein （a） levels were independent risk factors for acute MI. Lipoprotein （ a ） elevation was an independent risk factor for 3-vessel disease. Conclusion Insulin resistance and high serum hsCRP level were associated with occurrence of acute MI and angiographic severity of coronary disease in patients with normal glucose tolerance.

Myocardial infarction with non-obstructive coronary arteries: A comprehensive review and future research directions

Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries(MINOCA).This acute coronary syndrome differs from type 1 myocardial infarction(MI)regarding patient characteristics,presentation,physiopathology,management,treatment,and prognosis.Two-thirds of MINOCA subjects present ST-segment elevation;MINOCA patients are younger,are more often female and tend to have fewer cardiovascular risk factors.Moreover,MINOCA is a working diagnosis,and defining the aetiologic mechanism is relevant because it affects patient care and prognosis.In the absence of relevant coronary artery disease,myocardial ischaemia might be triggered by an acute event in epicardial coronary arteries,coronary microcirculation,or both.Epicardial causes of MINOCA include coronary plaque disruption,coronary dissection,and coronary spasm.Microvascular MINOCA mechanisms involve microvascular coronary spasm,takotsubo syndrome(TTS),myocarditis,and coronary thromboembolism.Coronary angiography with non-significant coronary stenosis and left ventriculography are first-line tests in the differential study of MINOCA patients.The diagnostic arsenal includes invasive and non-invasive techniques.Medical history and echocardiography can help indicate vasospasm or thrombosis,if one finite coronary territory is affected,or specify TTS if apical ballooning is present.Intravascular ultrasound,optical coherence tomography,and provocative testing are encouraged.Cardiac magnetic resonance is a cornerstone in myocarditis diagnosis.MINOCA is not a benign diagnosis,and its polymorphic forms differ in prognosis.MINOCA care varies across centres,and future multi-centre clinical trials with standardized criteria may have a positive impact on defining optimal cardiovascular care for MINOCA patients.

Risk of ventricular arrhythmia in patients with myocardial infarction and non-obstructive coronary arteries and normal ejection fraction

AIM To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and nonobstructive coronary arteries(MINOCA)with normal ejection fraction(EF).METHODS This is an observational analysis of 131 MINOCA patients with normal EF.Three cardiac magnetic resonance(CMR)diagnosis classes were recognized according to the late gadolinium enhancement(LGE)pattern:Myocardial infarction(MI)(n=34),myocarditis(n=47),and"no LGE"(n=50).Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year.RESULTS Ventricular arrhythmia was observed in 18(13.8%)patients during hospitalization.The"no LGE"patients experienced fewer ventricular events than the MI and myocarditis patients[4.0%vs 26.5%and 14.9%,respectively(P=0.013)].There was no significant difference between the MI and myocarditis groups.On multivariate analysis,LGE transmural extent[OR=1.52(1.08-2.15),P=0.017]and ST-segment elevation[OR=4.65(1.61-13.40),P=0.004]were independent predictors of ventricular arrhythmic events,irrespective of the diagnosis class.Finally,no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year.CONCLUSION MINOCA patients with normal EF presented no 1-year cardiovascular events,irrespective of the CMR diagnosis class.LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.

Therapeutic imaging window of cerebral infarction revealed by multisequence magnetic resonance imaging An animal and clinical study

In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes （T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]） following cerebral infarction. The pathological changes were divided into three phases： early cerebral infarction, middle cerebral infarction, and late cerebral infarction. In the early cerebral infarction phase （less than 2 hours post-infarction）, there was evidence of intracellular edema, which improved after reperfusion. This improvement was defined as the ischemic penumbra. In this phase, a high DWI signal and a low apparent diffusion coefficient were observed in the right basal ganglia region. By contrast, there were no abnormal T2WI and T2FLAIR signals. For the middle cerebral infarction phase （2-4 hours post-infarction）, a mixed edema was observed. After reperfusion, there was a mild improvement in cell edema, while the angioedema became more serious. A high DWI signal and a low apparent diffusion coefficient signal were observed, and some rats showed high T2WI and T2FLAIR signals. For the late cerebral infarction phase （4-6 hours post-infarction）, significant angioedema was visible in the infarction site. After reperfusion, there was a significant increase in angioedema, while there was evidence of hemorrhage and necrosis. A mixed signal was observed on DWI, while a high apparent diffusion coefficient signal, a high T2WI signal, and a high T2FLAIR signal were also observed. All 86 cerebral infarction patients were subjected to T2WI, T2FLAIR, and DWI. MRI results of clinic data similar to the early infarction phase of animal experiments were found in 51 patients, for which 10 patients （10/51） had an onset time greater than 6 hours. A total of 35 patients had MRI results similar to the middle and late infarction phase of animal experiments, of which eight patients （8/35） had an onset time less than 6 hours. These data suggest that defining the ＂therapeutic time window＂ as the time 6 hours after infarction may not be suitable for all patients. Integrated application of MRI sequences including T2WI, T2FLAIR, DW-MRI, and apparent diffusion coefficient mapping should be used to examine the ischemic penumbra, which may provide valuable information for identifying the ＂therapeutic time window＂.

Presentation and outcome of myocardial infarction with nonobstructive coronary arteries in coronavirus disease 2019

Among the cardiac complications of coronavirus disease 2019(COVID-19),one increasingly reported in the literature is myocardial infarction with nonobstructive coronaries(MINOCA).We reviewed all reported cases of MINOCA in COVID-19 patients to summarize its clinical features,evaluation,and treatment.We performed a literature search in Pubmed using the search terms‘COVID-19’and‘MINOCA’or‘non-obstructive coronaries’.Among the reported cases,the mean age was 61.5 years(SD±13.4),and 50%were men.Chest pain was the presenting symptom in five patients(62.5%),and hypertension was the most common comorbidity(62.5%).ST-elevation was seen in most patients(87.5%),and the overall mortality rate was 37.5%.MINOCA in COVID-19 is an entity with a broad differential diagnosis.Therefore,a uniform algorithm is needed in its evaluation to ensure timely diagnosis and management.

In-Hospital Cardiac Arrest after Emotional Stress in a Patient Hospitalized with Gastrointestinal Symptoms and Chronic Anxiety Disorder

Background:We report an acute emotional stress-induced in-hospital cardiac arrest in a patient admitted with gas-trointestinal symptoms after experiencing chronic anxiety disorder.Case Presentation:The patient was admitted to the Second Xiangya Hospital,Central South University,with gastrointestinal symptoms and chronic anxiety disorder,and experienced cardiac arrest during hospitalization after acute emotional stress.Malignant ventricular tachycardia and cardiogenic shock were evidenced in this patient after the acute emotional stress.Severe and extensive coronary spasm was confi rmed by emergency coronary angiography,and coronary spasm was relieved by intracoronary injection of nitroglycerin.The patient recovered from myocardial infarction with nonobstructive coronary arteries.However,the patient developed acute kidney dysfunction and severe pulmonary infection and eventually died of respiratory circulatory failure on the ninth day after the successful rescue.Conclusions:Acute emotional stress on top of chronic anxiety disorder in patients hospitalized for noncardiovascu-lar reasons might lead to the development of life-threatening cardiovascular diseases,including coronary artery spasm and myocardial infarction with nonobstructive coronary arteries.Psychological management is of importance to im-prove the outcome of these patients.

Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

BACKGROUND: Ankle brachial index (ABI) is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes mellitus (DM); however, the application in cerebral infarction (CI) is rare. OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease (PAD), compare metabolic characteristics of patients who having CI plus PAD or only having CI, and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb. DESIGN: Contrast observation based on CI patients. SETTING: Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region. PARTICIPANTS: A total of 124 CI patients were selected from Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006, including 72 males and 52 females aged from 45 to 88 years. All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination. All patients provided informed consent. There were 46 cases (37.2%) with CI plus PAD and 78 cases (62.8%) only with CI. METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor (GE Company). The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI. The normal ABI was equal to or more than 0.9. If ABI < 0.9 occurred at one side, patients were diagnosed as PAD. On the second morning after hospitalization, blood was collected to measure fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG2h), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Among them, blood glucose, lipid and other biochemical markers were measured with enzyme chemistry assay and HbA1c was measured with HbA1c meter based on high liquid phase. Measurement data and enumeration data were compared with t test and Chi-square test, and multiple factors were dealt with Logistic regression analysis and multivariate linear regression analysis. MAIN OUTCOME MEASURES: Results of correlation between ABI and metabolic markers with multivariate linear regression analysis; risk factors of CI plus PAD with Logistic regression analysis; comparisons of metabolic markers between PAD and non-PAD patients. RESULTS: All 124 patients with acute CI were involved in the final analysis. ① Comparisons of metabolic markers: Levels of serum LDL-C and uric acid (UA) were higher of PAD patients than those of non-PAD patients (t =2.051 9, 3.339 1, P < 0.05); however, there were no significant differences among other metabolic markers (P > 0.05). ② Results of multivariate linear regression analysis: PBG2h, LDL-C and UA were obvious correlation with ABI of posterior tibial artery of lower limb and dorsal pedis artery (partial regression coefficient = -0.231 to -1.010, P < 0.05). ③ Risk factors of CI plus PAD with Logistic regression analysis: Age, smoking history, sum of CI focus (≥3) and LDL-C were independent risk factor of CI plus PAD (OR =1.524-5.422, P < 0.05-0.01). CONCLUSION: ① Levels of serum LDL-C and UA of patients with CI plus PAD are high. ② ABI of lower limbs is correlation with PBG2h, LDL-C and UA. In addition, measuring ABI is beneficial for early diagnosing PAD of lower limbs of patients who have poorly controlled blood glucose, abnormal lipid and poor renal function. ③ Age, LDL-C and sum of CI focus (≥3) are independent risk factors of CI plus PAD. It is of significance for screening non-PAD patients to evaluate risk degrees and prognosis and select therapeutic methods based on ABI measurement.

Is Takotsubo cardiomyopathy still looking for its own nosological identity?

Despite several efforts to provide a proper nosological framework for Takotsubo cardiomyopathy(TCM),this remains an unresolved matter in clinical practice.Several clinical,pathophysiologic and histologic findings support the conceivable hypothesis that TCM could be defined as a unique pathologic entity,rather than a distinct subset of myocardial infarction with non-obstructive coronary arteries.Further investigations are needed in order to define TCM with the most appropriate disease taxonomy.

Decompressive craniectomy for malignant middle cerebral artery infarctions: a meta-analysis

Background: Decompressive craniectomy (DC) has been the classical management for malignant middle cerebral artery infarctions (mMCAI) in clinical practice. However, the association between DC and mMCAI remains unclear. This review went to evaluate the efficacy of DC in treating mMCAI patients. Methods: Studies were entirely searched since the foundation dates of multiple databases to June 2016. All major databases were involved, including Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and other sources. the bias risk of studies involved were evaluated. Modified Rankin Scale was defined as Primary outcome, Odds Ratio and 95% confidence intervals was taken as measurements. T2 (tau-squared) test, I2 test, and chi-square tests were used for statistical heterogeneity evaluation for each meta-analysis result, followed by fixed-effect model. Mantel-haenszel method was used in the process of summary estimations. All of the meta-analysis was conducted by Review Manager 5.3.Results & Conclusion: One thousand one hundred forty-five records of data were critically identified and collected through databases and 14 studies were finally involved. Result suggested that DC can ameliorate the suboptimal outcome of mMCAI patients.

Malignant middle-cerebral artery territory infarction in tuberculous vasculitis

Intracranial large vessel involvement is an unusual complication of tuberculous meningitis.The authors report a 39-year-old female presenting with an episode of seizure,followed by rapid decline in sensorium without prominent systemic features.An initial cranial magnetic resonance imaging revealed tuberculomata and patchy infarcts.Despite antituberculous therapy,she progressively worsened.A cranial computed tomography scan done following the worsening revealed a massive middle-cerebral artery(MCA)infarct.Unfortunately,the patient died in spite of decompressive craniotomy.Malignant MCA territory infarct is a rare and potentially fatal complication of tuberculous meningitis.

MECHANISMS INVOLVED IN THE REDUCTION OF INFARCT SIZE BY ACE INHIBITIOR AFTER LEFT CORONARY ARTERY LIGATION IN RATS

The contribution of the inhibition of angiotensin Ⅱ (ANGⅡ) synthesis and bradykinin (BK) breakdown to the effects of ACE inhibition on infarct size, cardiac hypertrophy and blood supply to the marginal zone of the infarcted area

Coronary artery dissection and acute myocardial infarction after blunt chest trauma

Coronary artery dissection and acute myocar-dial infarction（AMI） after blunt chest trauma （BCT） has rarely been reported1＇2. This report describes two cases of the left anterior de-scending（LAD） artery dissection and AMI after BCT, successfully treated with percutaneous coronary intervention （PCI） and they dis-charged without complications.

Atrioventricular block complicating inferior acute myocardial infarction treated with thrombolytic therapy

Objective To investigate the influence and mechanism of incidence of atrioventricular block (AVB) treated with thrombolytic therapy in acute inferior myocardial infarction (AIMI).Methods A total of 46 patients with AIMI were divided into the thrombolytic group (n = 23) and the nonthrornboytic group (n = 23). Intravenous or intracoronary urokinase was given to the former group. We observed the advancing courses of AVB, and further assessed the relationship between occurrence of AVB and stenosis of infarct-related artery (IRA) with coronary angiography.Results Two cases died of Ⅲ o AVB in the non-thrombolytic group, but none was found in the thrombolytic group. The occurrence rate of AVB was similar in both groups; but that of Ⅲ ° AVB was much lower in the thrombolytic group (4 cases) than that in the non-thrombolytic group (11 cases, P ＜ 0.05), and the duration of AVB decreased from 201 ± 113 hours to 102±60 hours after thrombolytic therapy ( P＜0.01 ),which was mainly due to the decrease of AVB in the vanishing interval, but not in the developing interval.The coronary angiography demonstrated that there were an increasing reperfusion flow and a decreasing coronary stenosis of the infarct-related artery after thrombolytic therapy.Conclusion Thrombolytic therapy can reduce the incidence of severe AVB, shorten its duration and decrease the mortality by increasing the coronary reperfusion flow in the patients with AIMI.

Effect of electroacupuncture on expressions of VEGF and CD31 in MCAO model rats

Objective： To investigate the effect of electroacupuncture （EA） at Ganshu （BL 18） and Shenshu （BL 23） on vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule-1 （PECAM-1）/CD31 around the cerebral infarction focus in middle cerebral artery occlusion （MCAO） rats and the possible mechanism, thus to provide a new strategy for the treatment of cerebral ischemic stroke by acupuncture. Methods： A total of 180 healthy male Sprague-Dawley （SD） rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, 45 rats in each group. MCAO model was established using the modified line-embolus method in all rats except for those in the sham operation group; rats in the acupoint group were treated with EA at Ganshu （BL 18） and Shenshu （BL 23）; rats in the non-acupoint group were treated with EA at the control points; rats in other 2 groups were only subjected to bundling without treatment. Ten rats in each group were randomly selected on the 3rd day, the 14th day and the 21st day after acupuncture stimulation to test the neurological function impairment. The expression levels of CD31 and VEGF were also detected. Results： Compared with the model group and non-acupoint group, the neurological function score of the acupoint group was decreased at each time point, and the differences were statistically significant （P〈0.05, P〈0.01）. The expressions of VEGF and CD31 in each group were the lowest on the 3rd day, reached the peak on the 14th day and still remained at high level on the 21st day. And the differences among groups were statistically significant both on the 14th day and the 21st day （P〈0.05, P〈0.01）. Compared with the model group and the non-acupoint group, the expressions of VEGF and CD31 in the acupoint group were increased, and the differences were statistically significant （all P〈0.05）. Conclusion： EA at Ganshu （BL 18） and Shenshu （BL 23） can significantly improve the neurological function score of MCAO model rats, and shows protective effect on cerebral ischemia. The protective mechanism may be related to the up-regulation of CD31 and VEGF expression around the cerebral infarction focus in the MCAO model rats and induction of angiogenesis.

Effect of electroacupuncture at Ganshu(BL 18) and Shenshu(BL 23) on the expression of EphB2 protein in cortex around cerebral infracted area of rat

Objective： To observe the effect of electroacupuncture （EA） on the expression of erythropoie-tin-producing hepatocyte receptor B2 （EphB2） in the cortex around the infracted area of middle cerebral artery occlusion （MCAO） rats at different timing, and to reveal the possible mechanism of acupuncture in the treatment of cerebral ischemia. Methods： A total of 180 male Sprague-Dawley （SD） rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, with 45 rats in each group. Rats in each group were further divided into three subgroups： postoperative 3 d, postoperative 14 d and postoperative 2l d groups, with 15 rats in each subgroup. The MCAO model was made by the modified occlusion method. The neurological function score, 2,3,5-triphenyl tetrazolium chloride （TFC） staining, immunohistochemistry assay, immunofluorescence double labeling method and Western blot were used to detect the corresponding indicators. Results： The neurological impairment of rats was most obvious at postoperative 3 d, and then gradually improved with time, which was more significant in the acupoint group （P〈0.05）. The change of infarcted volume was consistent with the neurological function impairment. The number of EphB2 positive cells （EphB2＋） around the infarcted area was decreased significantly at postoperative 3 d, and then gradually improved with time, which returned to the same level as that in the sham operation group at postoperative 21 d. The increase was most significant in the acupoint group （P〈0.05）, and the positive cell number was higher than that in the sham operation group （P〈0.01）. Western blot and immunohistochemistry results were basically consistent. Immunofluorescence displayed that EphB2＋ and postsynaptic density-95 positive （PSD-95＋） were co-expressed, after the MCAO operation, in the cortical neuron around the infracted area, and the number of co-expressing cells was increased gradually with time, which was most significant in the acupoint group （P〈0.05）. Conclusion： Electroacupuncture at Ganshu （BL 18） and Shenshu （BL 23） can significantly improve the neurological function and cerebral infarcted volume ratio of MCAO rats, which may be related to the activation of EphB2 expression in cortex around the infracted area and the promotion of synaptic remodeling.

Effcacy-oriented compatibility for Tianma(Rhizoma Gastrodiae),Yanlingcao(Trillium tschonoskii Maxim) and Bingpian(Borneolum Syntheticum) on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods

OBJECTIVE:To evaluate the compatibility of Tianma(Rhizoma Gastrodiae,TM),Yanlingcao(Trillium tschonoskii Maxim,YLC)and Bingpian(Borneolum Syntheticum,BP),and their efficacy in the treatment of cerebral ischemic stroke.METHODS:Network pharmacology was used to determine the compatibility of TM,YLC,and BP,and their potential mechanism.The middle cerebral artery occlusion(MCAO)rat model was used to evaluate the curative effect of the six combinations of TM,YLC,and BP(TZB1-TZB6)on cerebral ischemia,by using the weight matching method to form.The potential component changes of TM and YLC in the blood and brains of rats were analyzed using ultra performance liquid chromatography-mass spectrometry.Finally,molecular docking linked the results of animal experiments and network pharmacology,determining the potential component contributors of TM and YLC to treating ischemic stroke.RESULTS:TZB reduced the cerebral infarct volume and protected the nerve cells in MCAO rats.The components of TM and YLC were also identified in the blood and brain homogenate,and BP can facilitate the entry of the components of TM and YLC into the blood and brain.Diosgenin,pennogenin,and gastrodin induced effective binding activities with adenosine receptor a1.CONCLUSION:We investigate an approach that improves the means of folk prescription combined with multi technology that maybe promote the transformation of Chinese medicinal prescription into component-based Chinese medicine.