Secreted frizzled-related protein 2 ameliorates diabetic cardiomyopathy by activating mitophagy.

OBJECTIVES: Secreted frizzled-related protein 2 (SFRP2), a novel adipokine that used to be considered an inhibitor of the canonical Wnt pathway, may play a protective role in metabolic disorders. However, its effect on diabetic cardiomyopathy was still unclear. Accumulating evidence indicates that mitophagy can protect cardiac function in the diabetic heart. The present study aimed to explore the roles of SFRP2 on diabetic cardiomyopathy, focusing on the effects and mechanisms for regulating mitophagy. METHODS: Wild-type H9c2 cells, Sfrp2 overexpression and knockdown H9c2 cells were exposed to a glucolipotoxic milieu. Reactive oxygen species (ROS) production, cell viability, apoptosis, mitophagy and lysosomal activity were detected. The interaction of SFRP2 with frizzled 5 (FZD5), and its effect on expression and intracellular localization of transcription factor EB (TFEB) and ß-catenin were also explored. Diabetic rats and Sfrp2 overexpression diabetic rats were constructed to further document the findings from the in vitro study. RESULTS: The expression of SFRP2 was low and mitophagy was inhibited in H9c2 cells in a glucolipotoxic milieu. Sfrp2 overexpression activated mitophagy and reduced H9c2 cells injury, whereas Sfrp2 deficiency inhibited mitophagy and worsened this injury. Consistent with the in vitro findings, Sfrp2 overexpression ameliorated the impairment in cardiac function of diabetic rats by activating mitophagy. Sfrp2 overexpression upregulated the expression of calcineurin and TFEB, but did not affect ß-catenin in vitro and in vivo. The calcineurin inhibitor tacrolimus can inhibit mitophagy and worsen cell injury in Sfrp2 overexpression H9c2 cells. Furthermore, we found that FZD5 is required for the SFRP2-induced activation of the calcineurin/TFEB pathway and interacts with SFRP2 in H9c2 cells. Transfection with small interfering RNA targeting FZD5 opposed the effects of Sfrp2 overexpression on mitophagy and cell survival in a glucolipotoxic environment. CONCLUSIONS: SFRP2 can protect the diabetic heart by interacting with FZD5 and activating the calcineurin/TFEB pathway to upregulate mitophagy in H9c2 cells.

Associations of Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease With Cardiovascular Healthy Outcomes.

BACKGROUND: The role of nonalcoholic fatty liver disease (NAFLD) as a mediator in the association between various unhealthy lifestyles and major adverse cardiovascular events and all-cause death remains unclear. METHODS AND RESULTS: This study used data from the UK Biobank, with follow-up until the end of 2021. It involved the calculation of unweighted and weighted lifestyle scores using the Cox model to classify participants on the basis of these scores. Additionally, the research assessed the mediation effect proportion of NAFLD using the difference method and examined the interaction and joint effects of lifestyle and NAFLD on health outcomes. Among the 134 616 enrolled participants, 4024 had records of major adverse cardiovascular events, while among the 130 144 participants included in the analysis of all-cause death, 6697 deaths occurred. The proportions of the association between overall lifestyle and major adverse cardiovascular events mediated by NAFLD were 19.4% and 21.7% (95% CI, 16.2-22.6 and 17.8-25.7) for scores 1 and 2, respectively, and those for all-cause death were 14.1% and 10.1% (95% CI, 11.3-17.1 and 7.9-12.2). After fully adjusting for traditional cardiovascular risk factors, the mediating effects declined across both outcomes. The associations between overall lifestyle and outcomes were stronger among those of the non-NAFLD group, and significant interactions were observed between overall lifestyle and NAFLD status. The joint analysis revealed that patients with NAFLD with unhealthy lifestyle had the highest risk of major adverse cardiovascular events and all-cause death. CONCLUSIONS: Improving lifestyle and addressing metabolic risk factors are essential for cardiovascular risk management in patients with NAFLD.

Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury.

With the worldwide pandemic of metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD), cardiometabolic disease (CMD) has become a significant cause of death in humans. However, the pathophysiology of metabolic-associated cardiac injury is complex and not completely clear, and it is important to explore new strategies and targets for the treatment of CMD. A series of pathophysiological disturbances caused by metabolic disorders, such as insulin resistance (IR), hyperglycemia, hyperlipidemia, mitochondrial dysfunction, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy dysfunction, calcium homeostasis imbalance, and endothelial dysfunction, may be related to the incidence and development of CMD. Transcription Factor EB (TFEB), as a transcription factor, has been extensively studied for its role in regulating lysosomal biogenesis and autophagy. Recently, the regulatory role of TFEB in other biological processes, including the regulation of glucose homeostasis, lipid metabolism, etc. has been gradually revealed. In this review, we will focus on the relationship between TFEB and IR, lipid metabolism, endothelial dysfunction, oxidative stress, inflammation, ERS, calcium homeostasis, autophagy, and mitochondrial quality control (MQC) and the potential regulatory mechanisms among them, to provide a comprehensive summary for TFEB as a potential new therapeutic target for CMD.

Non-alcoholic fatty liver disease is associated with a worse prognosis in patients with heart failure: A pool analysis.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of heart failure (HF) than those without NAFLD. However, the prognostic impact of NAFLD in HF is still controversial. This meta-analysis aimed to explore the association between NAFLD and the risk of adverse outcomes in patients with HF. Methods: We searched multiple electronic databases (Embase, PubMed, and Google Scholar) for potentially related studies up to June 30, 2022. Cohort studies reported multivariable adjusted relative risks and 95% confidence intervals (CIs) of adverse outcomes in HF patients with NAFLD comparing those without NAFLD were included for analysis. Results: A total of six studies involving 12,374 patients with HF were included for analysis, with a median follow-up duration of 2.5 years. The pooled analysis showed that HF patients with NAFLD were associated with a significantly increased risk of major composite adverse outcomes (HR 1.61, 95% CI 1.25-2.07), all-cause mortality (HR 1.66, 95% CI 1.39-1.98), and HF hospitalization or re-hospitalization (HR 1.71, 95% CI 1.03-2.86). Conclusion: NAFLD is associated with a worse prognosis in patients with HF. Effective screening and treatment strategies are needed to improve the prognosis in HF patients with NAFLD.

Helicobacter pylori infection and risk of cardiovascular disease.

BACKGROUND: Whether Helicobacter pylori (H. pylori) infection is associated with an increased risk of cardiovascular disease (CVD) remains controversial. This study aimed to investigate the association between H. pylori infection and the risk of CVD. METHODS: Potentially related studies were searched in the electronic databases, including PubMed, EMBASE and Cochrane Library, from inception to 31 August 2022. Observational cohort studies that reported the multivariable-adjusted relative risks (RRs) for composite CVD, CHD, stroke, or all-cause mortality associated with H. pylori infection were included in the meta-analysis, using random-effects models. RESULTS: Forty-one cohort studies with 230,288 participants were included. After a median follow-up duration of 6.3 years, H. pylori infection was associated with a mildly increased risk of composite CVD (RR 1.10, 95% CI 1.03, 1.18) and coronary heart disease (RR 1.10, 95% CI 1.02, 1.18) compared with those without H. pylori infection. No significant association was observed between H. pylori infection and risk of stroke (RR 1.08, 95% CI 0.94, 1.23) or all-cause mortality (RR 1.02, 95% CI 0.90, 1.16). Compared with cytotoxin-associated gene-A (CagA) negative H. pylori infection, the risk of CVD was significantly increased in patients with CagA positive H. pylori infection (RR 1.58, 95% CI 1.03, 2.41). CONCLUSIONS: Helicobacter pylori infection is associated with a mildly increased risk of CVD. It may be of great public health and clinical significance to screen H. pylori infection in patients with a high risk of CVD.

Stains therapy and the risk of all bleeding and intracranial hemorrhage: A meta-analysis of randomized controlled studies.

AIMS: Statins had been used as a cornerstone in the primary and secondary prevention of cardiovascular disease. Widespread attention had been given to the risk of bleeding, especially intracranial hemorrhage (ICH) in patients receiving statins therapy. This study aimed to determine whether statins treatment was associated with the risk of bleeding and ICH in randomized controlled trials (RCTs). MATERIALS AND METHODS: Electronic databases were searched for studies up to September 8, 2022. Articles from RCTs were included in the meta-analysis if they reported the bleeding events associated with the treatment of statins or placebo/nonstatin treatment. The risk ratios (RR) of total bleeding and ICH were pooled from the number of patients with each outcome in the statins and control groups from the included studies. RESULTS: Twenty-nine studies comprising 145,929 individuals (2437 incident bleeding cases) were included in the meta-analysis. After a median follow-up duration of 3.65 years, statins treatment was not associated with the risk of all bleeding (RR = 1.03, 95% CI 0.93-1.15). Furthermore, in 26 studies comprising 144,177 participants, after a median follow-up duration of 3.95 years, statins treatment was not associated with the risk of ICH (RR = 1.05, 95% CI 0.84-1.31). Although in the subgroup analysis with patients with prior stroke, statins treatment showed an increased risk of ICH (RR = 1.47, 95% CI 1.07-2.01), sensitivity analysis showed that the result was unstable, which may be mainly driven by the SPARCL study. CONCLUSIONS: Statins therapy is not associated with the risk of all bleeding and ICH. Although a mildly increased risk of ICH in patients with prior stroke is observed, which may be caused by chance finding and warrant further documentation.

Prevalence and Related Factors of White Coat Hypertension and Masked Hypertension in Shunde District, Southern China.

Background: White coat hypertension (WCH) and masked hypertension (MH) can increase the risk of target organ damage. Home blood pressure monitoring is an important method for detecting WCH and MH. However, the prevalence and related factors of WCH and MH in China have been rarely reported. Objective: To explore the prevalence and related factors associated with white coat hypertension (WCH) and masked hypertension (MH) in Shunde District, Southern China. Methods: This study recruited subjects from the Physical Examination Center in Shunde Hospital, Southern Medical University. Office blood pressure and home blood pressure values were collected using the home blood pressure monitor with telemedicine device and office blood pressure monitor, and the prevalence of WCH and MH was calculated by the values. Multivariate logistic regression was used to explore the related factors for WCH and MH. Results: Four-hundred and sixty-one participants (61% male), with an average age of 49 years, were included. The prevalence of WCH and MH was 5.1 and 15.2%, respectively. Multivariate logistic regression analysis showed that smoking (OR = 4.71, 95% CI = 1.05-21.15) and family history of coronary heart disease (OR = 4.51, 95% CI = 1.08-18.93) were associated with higher odds of WCH. The associated factors for higher odds of MH were smoking (OR = 2.83, 95% CI = 1.11-7.23), family history of hypertension (OR = 2.17, 95% CI = 1.11-4.26) and family history of coronary heart disease (OR = 2.82, 95% CI = 1.07-7.45). Conclusion: WCH and MH are highly prevalent in the Physical Examination Center in Shunde Hospital, Southern Medical University. We found smoking and family history of coronary heart disease were related factors for WCH, and smoking, family history of hypertension and coronary heart disease were associated with the odds of MH. Home blood pressure monitoring with a telemedicine device should be recommended to identity abnormal BP phenotype.

Effects of statins in primary and secondary prevention for venous thromboembolism events: A meta analysis.

OBJECTIVE: The associations between statins use and incidence or recurrence of venous thromboembolism (VTE) are controversial. We aimed to conduct a meta-analysis to reconcile the conflicting results. METHODS: We searched PubMed, Embase and Cochrane Library for studies published from database inception until May 31, 2021. Cohort studies and Randomized Controlled Trials that reported incidence or recurrence of VTE using statins compared with placebo or non-statins were included for meta-analysis. RESULTS: A total of 43 studies comprising over 8.6 million participants were included for analysis. The median follow-up duration was 38.1 months. Compared with no statins treatment, statins appeared to have a protective effect in primary prevention of VTE (RR 0.78, 95% CI 0.72-0.85), but significant heterogeneity was found among included studies (I2 = 81%). Statins was also associated with a 26% reduced risk of recurrent VTE (RR 0.74, 95% CI 0.70-0.78), even in patients receiving anticoagulant therapy (RR 0.77, 95% CI 0.65-0.92). In patients with a history of VTE, statins was associated with a reduced risk of bleeding and all cause mortality. The NNT of statins to prevent one case of VTE in the cancer population, and one case of recurrent VTE in patients with a history of VTE was 103.1 and 90.7 person-years respectively. CONCLUSION: In high-risk patients, statins treatment may reduce the incidence of VTE. Statins can also reduce the risk of recurrent VTE and all-cause mortality in patients with a history of VTE.

SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy.

BACKGROUND: The mitochondrial dynamics and mitochondrial biogenesis are essential for maintaining the bioenergy function of mitochondria in diabetic cardiomyopathy (DCM). Previous studies have revealed that secreted frizzled-related protein 2 (SFRP2) is beneficial against apoptosis and oxidative stress. However, no research has confirmed whether SFRP2 regulates oxidative stress and apoptosis through mitochondrial function in DCM. METHODS: Exposure of H9C2 cardiomyocytes in high glucose (HG) 25 mM and palmitic acid (PAL) 0.2 mM was used to simulate DCM in vitro. H9C2 cells with SFRP2 overexpression or SFRP2 knockdown were constructed and cultured under glucolipotoxicity or normal glucose conditions. An SD rat model of type 2 diabetes mellitus (T2DM) was generated using a high-fat diet combined with a low-dose STZ injection. Overexpression of SFRP2 in the rat model was generated by using an adeno-associated virus approach. CCK-8, TUNEL assay, and DHE staining were used to detect cell viability, and MitoTracker Red CMXRos was used to detect changes in mitochondrial membrane potential. We used qRT-PCR and western blot to further explore the mechanisms of SFRP2 regulating mitochondrial dynamics through the AMPK/PGC1-α pathway to improve diabetic cardiomyocyte injury. RESULTS: Our results indicated that SFRP2 was significantly downregulated in H9C2 cells and cardiac tissues in T2DM conditions, accompanied by decreased expression of mitochondrial dysfunction. The mitochondrial membrane potential was reduced, and the cells were led to oxidative stress injury and apoptosis. Furthermore, the overexpression of SFRP2 could reverse apoptosis and promote mitochondrial function in T2DM conditions in vitro and in vivo. We also found that silencing endogenous SFRP2 could further promote glucolipotoxicity-induced mitochondrial dysfunction and apoptosis in cardiomyocytes, accompanied by downregulation of p-AMPK. CONCLUSION: SFRP2 exerted cardioprotective effects by salvaging mitochondrial function in an AMPK-PGC1-α-dependent manner, which modulates mitochondrial dynamics and mitochondrial biogenesis, reducing oxidative stress and apoptosis. SFRP2 may be a promising therapeutic biomarker in DCM.

Mitophagy in Diabetic Cardiomyopathy: Roles and Mechanisms.

Cardiovascular disease is the leading complication of diabetes mellitus (DM), and diabetic cardiomyopathy (DCM) is a major cause of mortality in diabetic patients. Multiple pathophysiologic mechanisms, including myocardial insulin resistance, oxidative stress and inflammation, are involved in the development of DCM. Recent studies have shown that mitochondrial dysfunction makes a substantial contribution to the development of DCM. Mitophagy is a type of autophagy that takes place in dysfunctional mitochondria, and it plays a key role in mitochondrial quality control. Although the precise molecular mechanisms of mitophagy in DCM have yet to be fully clarified, recent findings imply that mitophagy improves cardiac function in the diabetic heart. However, excessive mitophagy may exacerbate myocardial damage in patients with DCM. In this review, we aim to provide a comprehensive overview of mitochondrial quality control and the dual roles of mitophagy in DCM. We also propose that a balance between mitochondrial biogenesis and mitophagy is essential for the maintenance of cellular metabolism in the diabetic heart.

Association between prediabetes and adverse outcomes in heart failure.

AIMS: Patients with heart failure (HF) and with diabetes experienced significantly worse outcomes than those without diabetes. However, data on the prognostic impact of prediabetes in HF are inconclusive. This meta-analysis aimed to explore the association between prediabetes and the risk of all-cause mortality and adverse cardiac outcomes in patients with HF. MATERIALS AND METHODS: We searched multiple electronic databases (PubMed, Embase and Google Scholar) for relevant studies up to 31 March 2021. Studies were included for analysis if multivariable adjusted relative risks of adverse outcomes were reported in patients with prediabetes and with HF compared with those with normoglycaemia. Random-effects models were used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Twelve studies comprising 28 643 patients with HF reported the risk of all-cause mortality and cardiac outcomes associated with prediabetes. The prevalence of prediabetes ranged from 9.6% to 37.2%. After a median follow-up duration of 2.3 years, patients with HF and with prediabetes were associated with an increased risk of all-cause mortality (HR 1.29, 95% CI 1.06-1.58), cardiovascular mortality (HR 1.59, 95% CI 1.09-2.32), HF hospitalization (HR 1.33, 95% CI 1.09-1.61), all-cause mortality and/or HF hospitalization (HR 1.22, 95% CI 1.01-1.47), as well as cardiovascular mortality and/or HF hospitalization (HR 1.21, 95% CI 1.07-1.37). CONCLUSIONS: Prediabetes is associated with a worse prognosis in patients with HF. Further risk stratification and effective treatment strategies are needed in patients with prediabetes and with HF to improve the prognosis.

Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension.

BACKGROUND: Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer's disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood. METHODS: The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. Enzyme-linked immunosorbent assays were used to examine plasma amyloid-beta (Aß)40, Aß42, and tau concentration in hypertensive patients. Metabolomics and metagenomics were performed to identify the significantly changed circulating metabolites and microbiota between healthy individuals and hypertensive patients. Pearson's correlation was used to examine the association between cognitive indicators and differential metabolites. RESULTS: We found significantly decreased MMSE scores, elevated plasma Aß40, and decreased Aß42/Aß40 ratio in hypertensive patients, which are critically associated with AD pathology. Based on metabolomics, we found that significantly altered metabolites in the plasma of hypertensive patients were enriched in the benzoate degradation and phenylpropanoid biosynthesis pathways, and they were also correlated with changes in MMSE scores and Aß42/Aß40 ratio. In addition, metabolomics signaling pathway analysis suggested that microbial metabolism was altered in hypertensive patients. We also identified altered blood microbiota in hypertensive patients compared with the controls. CONCLUSIONS: Our study provides a novel metabolic and microbial mechanism, which may underlie the cognitive impairment in hypertensive patients.

Prognostic Value of Secreted Frizzled-Related Protein 5 in Heart Failure Patients With and Without Type 2 Diabetes Mellitus.

BACKGROUND: Patients with heart failure (HF) with diabetes mellitus have distinct biomarker profiles compared with those without diabetes mellitus. SFRP5 (secreted frizzled-related protein 5) is an anti-inflammatory adipokine with an important suppressing role on the development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the prognostic value of SFRP5 in patients with HF with and without T2DM. METHODS: The study included 833 consecutive patients with HF, 312 (37.5%) of whom had T2DM. Blood samples were collected at presentation, and SFRP5 levels were measured. The primary outcome was the composite end points of first occurrence of HF rehospitalization or all-cause mortality during follow-up. RESULTS: During median follow-up of 2.1 years, 335 (40.2%) patients in the cohort experienced the composite primary outcome. After adjustment for multiple risk factors, each doubling of SFRP5 level was associated with a 21% decreased risk of primary outcomes in the overall study population (P<0.001). Subgroup analyses showed that the association between level of SFPR5 and primary outcomes may be stronger in patients with T2DM (hazard ratio, 0.69 [95% CI, 0.61-0.79]) than in patients without T2DM (hazard ratio, 0.89 [95% CI, 0.79-1.01]; interaction P=0.006). Similar associations were observed when taking SFRP5 as a categorical variable. Addition of SFRP5 significantly improved discrimination and reclassification of the incident primary outcomes beyond clinical risk factors and N-terminal pro-B-type natriuretic peptide in all patients with HF and those with T2DM (all P<0.01). CONCLUSIONS: SFRP5 is an independent novel biomarker for risk stratification in HF, especially in HF with T2DM.

Piwi-interacting RNAs play a role in vitamin C-mediated effects on endothelial aging.

The underlying mechanisms that mediate the effects of vitamin C on endothelial cell aging are widely unknown. To investigate whether Piwi-interacting RNAs (piRNAs) are involved in this process, an endothelial aging model was induced in vitro using H2O2 in human umbilical vein endothelial cells (HUVECs) and then treated with vitamin C (VC). Untreated HUVECs without H2O2 exposure were used to serve as the negative control group. Cell cycle, cell viability, and aging-associated protein expression were assessed, and RNA sequencing was performed to reveal the piRNA profile. Functional and regulatory networks of the different piRNA target genes were predicted by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis. H2O2 induced G1 phase cell arrest, decreased cell viability, and upregulated the senescence marker p16 in HUVECs. We found that VC treatment inhibited G1 phase cell arrest, increased the number of cells in the S and G2/M phases, increased cell viability, and decreased p16 expression. The piRNA expression profiles revealed that a large proportion of piRNAs that were differentially expressed in H2O2-treated HUVECs were partly normalized by VC. Furthermore, a number of piRNAs associated with the response to VC in H2O2-treated HUVECs were linked with senescence and cell cycle-related pathways and networks. These results indicate that the ability of VC to attenuate H2O2-mediated endothelial cell senescence may be associated with changes in expression of piRNAs that are linked to the cell cycle.

Circular RNA-protein interactions: functions, mechanisms, and identification.

Circular RNAs (circRNAs) are covalently closed, endogenous RNAs with no 5' end caps or 3' poly(A) tails. These RNAs are expressed in tissue-specific, cell-specific, and developmental stage-specific patterns. The biogenesis of circRNAs is now known to be regulated by multiple specific factors; however, circRNAs were previously thought to be insignificant byproducts of splicing errors. Recent studies have demonstrated their activity as microRNA (miRNA) sponges as well as protein sponges, decoys, scaffolds, and recruiters, and some circRNAs even act as translation templates in multiple pathophysiological processes. CircRNAs bind and sequester specific proteins to appropriate subcellular positions, and they participate in modulating certain protein-protein and protein-RNA interactions. Conversely, several proteins play an indispensable role in the life cycle of circRNAs from biogenesis to degradation. However, the exact mechanisms of these interactions between proteins and circRNAs remain unknown. Here, we review the current knowledge regarding circRNA-protein interactions and the methods used to identify and characterize these interactions. We also summarize new insights into the potential mechanisms underlying these interactions.

Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease.

The Wnt signaling pathway plays important roles in organ development and disease processes. Secreted frizzled-related protein 2 (sFRP2), a vital molecule of Wnt signaling, can regulate cardiac development and cardiovascular disease. Recent studies have suggested that sFRP2 is not only an antagonist of the canonical Wnt signaling pathway, but also has a more complex relationship in myocardial fibrosis, angiogenesis, cardiac hypertrophy and cardiac regeneration. Here, we review the role of sFRP2 and Wnt signaling in cardiac development and cardiovascular disease.

Clinical applications for out-of-office blood pressure monitoring.

Hypertension is one of the most common chronic diseases as well as the leading risk factor for cardiovascular disease (CVD). Efficient screening and accurate blood pressure (BP) monitoring are the basic methods of detection and management. However, with developments in electronic technology, BP measurement and monitoring are no longer limited to the physician's office. Epidemiological and clinical studies have documented strong evidence for the efficacy of out-of-office BP monitoring in multiple fields for managing hypertension and CVD. This review discusses applications for out-of-office BP monitoring, including home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM), based on recent epidemiological data and clinical studies regarding the following factors: the detection of abnormal BP phenotypes, namely, white coat hypertension and masked hypertension; stronger ability to determine the prognosis for target organ damage and mortality; better BP control; screening for hypotension; and unique approaches to identifying circadian BP patterns and BP variability.

IGF-1 enhances BMSC viability, migration, and anti-apoptosis in myocardial infarction via secreted frizzled-related protein 2 pathway.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising therapeutic strategy for ischemic heart disease. However, its effects are hampered by the poor viability of transplanted cells and the hostile microenvironment of the ischemic region. Insulin-like growth factor-1 (IGF-1) is an important paracrine growth factor of BMSC and plays an important role in the properties of BMSC. Here, we investigated whether overexpressing IGF-1 could enhance the BMSC viability, migration, anti-apoptosis, and protective effects of cardiomyocytes, and explore the underlying mechanisms' focus on the role of the AKT/secreted frizzled-related protein 2 (SFRP2)/ß-catenin pathway. METHODS: We constructed BMSCs overexpressing insulin-like growth factor-1 (BMSCs-IGF-1) or empty vector (BMSCs-NC) using lentivirus, and evaluated cell survival, proliferation, and migration under normoxic and hypoxic conditions. Co-culture of rat cardiomyoblasts with BMSCs was performed to explore the paracrine effect of BMSCs-IGF-1 for rescuing cardiomyoblasts under hypoxia. Transplantation of BMSCs in acute myocardial infarction rats was used to explore the effect of BMSCs-IGF-1 therapy. RESULTS: BMSCs-IGF-1 exhibited a higher cell proliferation rate, migration capacity, and stemness, and were more resistant to apoptosis under hypoxia. Overexpression of IGF-1 upregulated the expression of total and nuclear ß-catenin via the AKT-secreted frizzled-related protein 2 (SFRP2) pathway, which enhanced cell survival. Inhibition of AKT or SFRP2 knockdown by siRNA significantly antagonized the effect of IGF-1 and decreased the expression of ß-catenin. The expression of ß-catenin target genes, including cyclin D1 and c-Myc, were accordingly decreased. Moreover, BMSCs-IGF-1 could rescue cardiomyoblasts from hypoxia-induced apoptosis and preserve cell viability under hypoxia. Transplantation of BMSCs-IGF-1 into myocardial infarction rats greatly reduced infarct volume than BMSCs-NC, with significantly greater expression of SFRP2 and ß-catenin. CONCLUSIONS: These results suggest that in BMSCs overexpressing IGF-1, SFRP2 is an important mediator for the enhancement of stem cell viability via activating, rather than antagonizing, the Wnt/ß-catenin pathway.

A retrospective cohort study of oral anticoagulant treatment in patients with acute coronary syndrome and atrial fibrillation.

OBJECTIVE: To examine the real-world patterns of oral anticoagulant (OAC) therapy in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) in Southern China undergoing percutaneous coronary intervention (PCI) and determine the clinical characteristics associated with OAC prescription. DESIGN: A retrospective cohort study. SETTING: This study was conducted in the Shunde Hospital, Southern Medical University and the second hospital of Zhaoqing, China, from January 2013 to 31 December 2018. PARTICIPANTS: Patients were aged ≥18 years, hospitalised for ACS and received PCI treatment. OUTCOME MEASURES: AF was diagnosed based on an ECG recording or a Holter monitor. Prescription of OACs and antiplatelets were determined from the discharge medication list. RESULTS: A total of 3612 patients with ACS were included: 286 (7.9%) were diagnosed with AF, including 45 (1.2%) with paroxysmal AF, 227 (6.3%) with persistent/permanent AF and 14 (0.4%) with unclassified AF. Although 95.5% of patients with AF were at high risk (CHA2DS2-VASc score ≥2) of stroke, only 21.7% of them were discharged on OACs (10.5% received warfarin and 11.2% received non-vitamin K antagonist OACs). Patients with pre-admission use of OAC, a HAS-BLED score <3, with persistent/permanent AF were more likely to receive OAC treatment at discharge. CONCLUSION: We found that approximately 8% of patients who underwent PCI during ACS hospitalisation also demonstrated AF. Anticoagulant therapy was greatly underused. Patients with paroxysmal AF and an increased risk of bleeding were less likely to receive anticoagulant treatment. Further efforts should be made to increase the adherence to guideline recommendations for OACs.