PET evaluation of myocardial perfusion function after percutaneous coronary intervention in patients with chronic total occlusion: a systematic review and meta-analysis.

Objective. The benefit of percutaneous coronary intervention (PCI) in chronic complete coronary artery occlusion (CTO) remains controversial. PCI is currently indicated only for symptom and myocardial ischemia abolition, but large chronically occluded vessels with extensive afferent myocardial territories may benefit most from this procedure. The noninvasive evaluation of myocardial perfusion is critical before and after revascularization, and positron emission tomography (PET) can determine absolute myocardial perfusion. Here, we aimed to explore and compare myocardial perfusion in CTO territories and their remote associated areas before and after PCI. Design. We searched for relevant articles published before November 28, 2022, in the Cochrane Library and PubMed. We calculated 95% confidence intervals (CIs) and standardized mean differences (SMDs) for parameters related to myocardial perfusion in CTO territories and remote areas in CTO patients before and after PCI. Results. We included five studies published between 2017 and 2022, with a total of 592 patients. Stress myocardial blood flow (MBF) was increased in CTO territories after PCI when compared to pre-PCI (mean difference [MD]: 1.70, 95% confidence interval [CI] 1.33-2.08, p < 0.001). Coronary flow reserve (CFR) in CTO regions was also higher after PCI (MD 1.37,95% [CI]1.13-1.61, p < 0.001). Stress MBF in remote regions was also increased after PCI (MD 0.27,95% [CI]0.99 ∼ 0.45, p = 0.004), as was CFR in remote regions (MD 0.32,95% [CI] 0.14-0.5, p = 0.001). Conclusions. According to our pooled analysis of current literature, there was an increase in stress MBF and CFR in both CTOs and remote regions after PCI, suggesting that patients with CTO have widespread recovery of blood perfusion after the procedure. These results provide evidence that patients with CTO arteries and high ischemic burdens would indeed benefit from CTO-PCI. Future research on the correlation of ischemia burden reduction with hard clinical endpoints would contribute to a clearer demarcation of the role of CTO PCI with prognostic potential.

HbA1c is related to microcirculation blood perfusion in patients with coronary microvascular disease using stress perfusion cardiac magnetic resonance: An observational study.

BACKGROUND: In coronary microvascular disease (CMD) patients, the incidence of major adverse cardiovascular events (MACEs) in patients with myocardial perfusion reserve index (MPRI) ≤ 1.47 is three times higher than that in MPRI > 1.47. We investigated whether the increase of glycated hemoglobin A1c (HbA1c) could increase the risk of MPRI ≤1.47 in diabetic and non-diabetic patients. METHODS: From November 2019, patients with ischemic symptoms but without obstructive coronary disease were screened. Use MPRI measured by stress perfusion cardiac magnetic resonance (CMR) to reflect microcirculation blood perfusion, and MPRI <2.5 were included. The patients were divided into two groups based on MPRI was greater or <1.47. The risk factors for CMD were explored using logistic regression analysis. RESULTS: A total of 80 patients with an MPRI of 1.69 ± 0.79 were included. CMD patients with an MPRI of ≤1.47(n = 33) were higher than MPRI of >1.47(n = 47) in age, presence of diabetes mellitus, fasting blood glucose levels and HbA1c levels (P < 0.05). In non-diabetic patients, increased HbA1c was associated with the risk of MPRI≤1.47 (OR = 0.017, 95%CI: 0.050-1.107, P = 0.045). Compared with non-diabetic patients with HbA1c < 6.0, non-diabetic patients with HbA1c ≥ 6.0 increased the risk of MPRI of ≤1.47 (OR = 0.219, 95%CI: 0.069-0.697, P = 0.010). In diabetic patients, HbA1c was not associated with the risk of MPRI of ≤1.47 (OR = 1.043, 95%CI: 0.269, 4.044, P = 0.952). And compared with non-diabetic patients with HbA1c <6.0, diabetic patients with HbA1c <6.0 (OR = 0.917, 95%CI: 0.233-3.610, P = 0.901) or ≥6.0 (OR = 0.326, 95%CI: 0.073-1.446, P = 0.140), the risk of MPRI ≤ 1.47 was not further increased. CONCLUSIONS: In non-diabetic patients, elevated HbA1c is related to MPRI≤1.47(a value increased incidence of MACEs). Therefore, in patients with undiagnosed diabetes, early management of glycosylated hemoglobin is very important. TRIAL REGISTRATION: This clinical trial has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR1900025810.

Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin pathway modulation.

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.

Inclusion of quantitative high-density plaque in coronary computed tomographic score system to predict the time of guidewire crossing chronic total occlusion.

OBJECTIVE: This study aimed to establish a new scoring system that includes histological quantitative features derived from coronary computed tomographic angiography (CCTA) to predict the efficiency of chronic total occlusion percutaneous coronary intervention (CTO-PCI). METHODS: This study analyzed clinical, morphological, and histological characteristics of 207 CTO lesions in 201 patients (mean age 60.0 [52.0-65.0] years, 85% male), which were recruited from two centers. The primary endpoint was a guidewire successfully crossing the lesions within 30 m. The new predictive model was generated by factors that were determined by multivariate analysis. The CCTA plaque (CTAP) score that included a quantitative plaque characteristic was developed by assigning an appropriate integer score to each independent predictor, then summing all points. In addition, the CTAP score was compared with other predictive scores based on CCTA. RESULTS: The endpoint was achieved in 63% of the lesions. The independent predictors included previous CTO-PCI failure, the proximal blunt stump, proximal side branch, distal side branch, occluded segment bending > 45°, and high-density plaque volume (fibrous volume + calcified volume) ≥ 19.9 mm3. As the score increased from 0 to 5, the success rate of the guidewire crossing within 30 m decreased from 96 to 0%. Comparing the CTAP score with other predictive scores, the CTAP score showed the highest discriminant power (c-statistic = 0.81 versus 0.73-0.77, p value 0.02-0.07). The CTAP score showed similar results for procedural success. CONCLUSION: The CTAP score efficiently predicted the guidewire crossing efficiency and procedural success. KEY POINTS: • An increase in high-density plaque volume (fibrous + dense calcium) was more probable to reduce the efficiency of crossing and lead to procedural failure. • The new prediction scoring system with the addition of the quantitative characteristics of plaques had an improved predictive ability compared with the traditional prediction scoring system.

Staged complete revascularization or culprit-only percutaneous coronary intervention for multivessel coronary artery disease in patients with ST-segment elevation myocardial infarction and diabetes.

BACKGROUND: Recently, several randomized trials have noted improved outcomes with staged percutaneous coronary intervention (PCI) of nonculprit vessels in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, it remains unclear whether diabetes status affects the outcomes after different revascularization strategies. This study thus compared the impact of diabetes status on long-term outcomes after staged complete revascularization with that after culprit-only PCI. METHODS: From January 2006 to December 2015, 371 diabetic patients (staged PCI: 164, culprit-only PCI: 207) and 834 nondiabetic patients (staged PCI: 412, culprit-only PCI: 422) with STEMI and multivessel disease were enrolled. The primary endpoint was 5-year major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction (MI), stroke or unplanned revascularization. RESULTS: The rate of the 5-year composite primary endpoint for diabetic patients was close to that for nondiabetic patients (34.5% vs. 33.7%; adjusted hazard ratio [HR] 1.012, 95% confidence interval [CI] 0.815-1.255). In nondiabetic patients, the 5-year risks of MACCE (31.8% vs. 35.5%; adjusted HR 0.638, 95% CI 0.500-0.816), MI (4.6% vs. 9.2%; adjusted HR 0.358, 95% CI 0.200-0.641), unplanned revascularization (19.9% vs. 24.9%; adjusted HR 0.532, 95% CI 0.393-0.720), and the composite of cardiac death, MI or stroke (11.4% vs. 15.2%; adjusted HR 0.621, 95% CI 0.419-0.921) were significantly lower after staged PCI than after culprit-only PCI. In contrast, no significant difference was found between the two groups with respect to MACCE, MI, unplanned revascularization, and the composite of cardiac death, MI or stroke in diabetic patients. Significant interactions were found between diabetes status and revascularization assignment for the composite of cardiac death, MI or stroke (Pinteraction = 0.013), MI (Pinteraction = 0.005), and unplanned revascularization (Pinteraction = 0.013) at 5 years. In addition, the interaction tended to be significant for the primary endpoint of MACCE (Pinteraction = 0.053). Moreover, the results of propensity score-matching analysis were concordant with the overall analysis in both diabetic and nondiabetic population. CONCLUSIONS: In patients with STEMI and multivessel disease, diabetes is not an independent predictor of adverse cardiovascular events at 5 years. In nondiabetic patients, an approach of staged complete revascularization is superior to culprit-only PCI, whereas the advantage of staged PCI is attenuated in diabetic patients. Trial registration This study was not registered in an open access database.

Stent Versus Non-Stent in Treating Intermediate Stenosis Culprit Lesions in Acute ST-Segment Elevation Myocardial Infarction Patients.

To investigate the efficacy and safety of stent versus non-stent in treating acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel disease and intermediate stenosis culprit lesions.Between September 2009 and May 2015, 475 acute STEMI patients (time from symptom onset < 12 hours) with single vessel disease and intermediate stenosis culprit lesions were retrospectively studied at Beijing Anzhen Hospital. The patients were divided into a stent group (n = 308) and non-stent group (n = 167) based on whether they received stent implantation or not during primary coronary angiography.During follow-up, the stent group patients had a lower major adverse cardiac and cerebrovascular event (MACCE) rate than the non-stent group: 5.5% versus 12.0%; P = 0.01; hazard ratio (HR) 0.35 [95% confidence interval (CI): 0.180.69]). The nonfatal myocardial infarction (MI) rate was lower in the stent group (2.9% versus 7.2%, P = 0.03). The cardiac death rate (1.9% versus 3%, P = 0.45) and stroke (0.6% versus 1.8%, P = 0.35) rate were similar between the stent and non-stent groups. The two groups shared similar all cause death rates: 4.9% versus 5.4%, respectively, P = 0.81; HR: 1.23 [95%CI: 0.51-2.99]. The composite ischemia outcome of death/MI/stroke was lower in the stent group (8.1% versus 14.4%, P = 0.02). The stent and non-stent groups had similar repeat revascularization rates (10.1% versus 11.4%, P = 0.67); ischemia driven readmission (19.5% versus 15.0%, P = 0.27), and bleeding (1.3% versus 1.2%, P = 1) rates.Stent implantation has a better efficacy and safety in reducing adverse ischemia events in acute STEMI patients with single vessel disease and intermediate stenosis culprit lesions.

[Effect and mechanism of recombinant hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice].

OBJECTIVE: To explore the effect and mechanism of hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice. METHODS: Totally 24 ApoE(-/-) mice, 7-8 weeks old were fed with high fat diets. They were randomly divided into the recombinant hirudin treatment group (drug group) and the model group according to body weight and different dens, 12 in each group. Twelve C57BL/6J mice, 7-8 weeks old fed with high fat diet were recruited as the normal control group. Recombinant hirudin (0.25 mg/kg) was intraperitoneally injected to mice in the drug group from the 10th week old once every other day for five successive weeks. Equal volume of normal saline was injected to mice in the model group. Mice in the normal control group received no treatment. All mice were sacrificed after fed with high fat diet until they were 20 weeks old. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), high-sensitive C-reactive protein (hs-CRP), E-selectin, interleukin-6 (IL-6), and stromal metalloproteinase-2 (MMP-2) were detected. The plaque/lumen area and extracellular lipid composition/ plaque area were analyzed by HE staining and morphometry. Changes of signaling molecules in store-operated calcium channels, including stromal interacting molecule 1 (STIM1), Orail protein, and transient receptor potential channel 1 (TRPC1) were determined by Western blot. Results Lipid plaque formed in the aorta vessel wall of 20-week old mice in the model group. Compared with the normal control group, serum levels of TC, TG and LDL increased (P<0.01), hs-CRP, E-selction, IL-6, and MMP-2 obviously increased (P<0.01, P<0.05) in the model group; expression levels of STIM1, TRPC1, and Orail significantly increased (P<0.01). Compared with the model group, the plaque/lumen area and the extracellular lipid composition/plaque area significantly decreased in the drug group (P<0.05, P<0.01); serum levels of TC and LDL, hs-CRP, E-selction, IL-6, and MMP-2 obviously decreased (P<0.05, P<0.01); expression levels of STIM1, TRPC1, and Orail were significantly down-regulated (P<0.05, P<0.01). CONCLUSION: Hirudin could significantly improve lipids and endothelial functions of ApoE(-/-) mice, down-regulate expression levels of STIM1, Orai1, and TRPC1, and thus delaying the occurrence and development of atherosclerosis.

Causal Relationships between Lymphocyte Subsets and Risk of Coronary Artery Disease: A Two-Sample Mendelian Randomization Study.

Background: Currently, the causal relationship between lymphocyte subsets and coronary artery disease (CAD) remains unclear. Therefore, we utilized Mendelian randomization (MR) to assess the association between lymphocyte subsets and CAD. Methods: We performed a two-sample MR analysis using publicly available genome-wide association studies (GWAS) datasets. The primary method of analysis to comprehensively evaluate causal effects was the inverse variance-weighted (IVW) method. The four additional MR approaches were MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analysis incorporated Cochran's Q and MR-Egger intercept tests to identify residual heterogeneity and potential horizontal pleiotropy, respectively. The MR-PRESSO distortion test was applied to identify potential pleiotropic outliers. Leave-one-out analysis confirmed that no single single-nucleotide polymorphism (SNP) significantly affected the MR estimate. We conducted reverse MR analysis to investigate the impact of variables correlated with outcomes in forward MR analysis. Results: The IVW method revealed a significant positive association between B cell count and CAD (odds ratio (OR) = 1.08 (95% CI: 1.04, 1.11), p = 2.67 × 10-5). A similar association was observed between B cell count and myocardial infarction (MI) (OR = 1.07 (95% CI: 1.03, 1.11), p = 5.69 × 10-4). Sensitivity analyses detected no outliers, heterogeneity, or pleiotropy. The reverse MR analysis was conducted to investigate the impact of CAD and MI on B cell count, and the IVW results showed no statistical significance. Conclusions: Our study suggests that a higher absolute B cell count is linked to an increased risk of CAD and MI.

Drug-Coated Balloon-Only Strategy for De Novo Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials.

Backgrounds: Many clinical trials have demonstrated the value of drug-coated balloons (DCB) for in-stent restenosis. However, their role in de novo lesions is not well documented. The aim of this study is to evaluate the safety and efficacy of the DCB-only strategy compared to other percutaneous coronary intervention strategies for de novo coronary lesions. Methods: The PubMed, Embase, Web of Science, and Cochrane Library Central Register of Controlled Trials (CENTRAL) electronic databases were searched for randomized controlled trials published up to May 6, 2023. The primary outcomes were major adverse cardiac events and late lumen loss. Results: A total of eighteen trials with 3336 participants were included. Compared with drug-eluting stents, the DCB-only strategy was associated with a similar risk of major adverse cardiac events (risk ratio (RR) = 0.90; 95% confidence interval (CI): 0.59 to 1.37, P = 0.631) and a significant decrease in late lumen loss (standardized mean difference (SMD) = -0.29, 95% CI: -0.53 to -0.04, P = 0.021). This effect was consistent in subgroup analysis regardless of indication, follow-up time, drug-eluting stent type, and dual antiplatelet therapy duration. However, DCBs were inferior to DESs for minimum lumen diameter and percentage diameter stenosis. The DCB-only strategy showed significantly better outcomes for most endpoints compared to plain-old balloon angioplasty or bare metal stents. Conclusions: Interventions with a DCB-only strategy are comparable to those of drug-eluting stents and superior to plain-old balloon angioplasty or bare metal stents for the treatment of selected de novo coronary lesions. Additional evidence is still warranted to confirm the value of DCB before widespread clinical utilization can be recommended.

Evaluation of left ventricular diastolic function in patients with coronary microvascular dysfunction via cardiovascular magnetic resonance feature tracking.

Background: Coronary microvascular dysfunction (CMD) has been suggested to be one of the pathologic mechanisms contributing to heart failure with preserved left ventricular ejection fraction (LVEF) and left ventricular (LV) diastolic dysfunction. We therefore aimed to evaluate LV diastolic function in patients with CMD using cardiovascular magnetic resonance feature tracking (CMR-FT). Methods: We prospectively enrolled 115 patients referred to cardiology clinics for chest pain assessment who subsequently underwent coronary computed tomography angiogram and stress perfusion CMR. CMD was defined as the presence of subendocardial inducible ischemia detected through visual assessment. LV diastolic function was evaluated using CMR-derived volume-time curves and CMR-FT parameters. The former included early peak filling rate (PFR) and time to PFR; the latter included LV global/regional peak longitudinal diastolic strain rate (LDSR), circumferential diastolic strain rate (CDSR), and radial diastolic strain rate (RDSR). Results: A total of 92 patients with 1,312 segments were eventually included. Of these, 19 patients were classified as non-CMD (48.8±11.2 years; 63.2% male) and 73 as with CMD (52.3±11.9 years; 54.8% male). The LVEFs were similar and preserved in both groups (P=0.266). At the per-patient level, no differences were observed in PFR, time to PFR, or LV global diastolic strain rates between the two groups. At the per-segment level, 51% (665/1,312) of the myocardial segments were classified as CMD, whereas 49% (647/1,312) were classified as non-CMD. CMD segments showed significantly lower regional CDSR (P=0.019) and RDSR (P=0.006) compared with non-CMD segments. Conclusions: Despite normal LV ejection fraction in CMD patients, decreased LV diastolic function in CMD myocardial segments indicates early diastolic impairment.

Regulation of cardiovascular and cardiac functions by caveolins.

Caveolae are intracellular vesicles with diameters ranging from 50 to 100 nm. The role of caveolins in mediating oxidative stress, autophagy, apoptosis, fibrosis, and vascular remodeling has attracted increasing attention in cardiovascular therapy. Several studies have suggested that caveolin could be a therapeutic target for the treatment of cardiac and/or vascular injury via several pathophysiological mechanisms. Despite substantial advances in our understanding of the basic biology of vesicles over the past decade, the relevance and specific role of these mechanisms in cardiovascular homeostasis remains ambiguous. Here, we review the macroscopic role of caveolins in protecting cardiac function and, at the microscopic level, examine possible cardioprotective caveolar mechanisms, including their antioxidative stress, antiapoptosis, autophagy-regulatory, antifibrosis, and angiogenesis-promoting properties. We believe that the role of caveolins in cardiac functioning has not been fully elucidated and is an important line of future research with several cardioprotective implications.

The cGAS-STING Pathway: A Ubiquitous Checkpoint Perturbing Myocardial Attributes.

As an innate immune route of defense against microbial infringement, cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)- stimulator of interferon genes (STING) signaling does not simply participate in amplifying inflammatory responses via releasing type-I interferon (IFN) or enhance the expression of pro-inflammatory genes, but also interplays with multifarious pathophysiological activities, such as autophagy, apoptosis, pyroptosis, ferroptosis, and senescence in a broad repertoire of cells like endothelial cells, macrophages and cardiomyocyte. Thus, the cGAS-STING pathway is closely linked with aberrant heart morphologically and functionally via these mechanisms. The past few decades have witnessed an increased interest in the exact relationship between the activation of the cGAS-STING pathway and the initiation or development of certain cardiovascular diseases (CVD). A group of scholars has gradually investigated the perturbation of myocardium affected by the overactivation or suppression of the cGAS-STING. This review focuses on how the cGAS-STING pathway interweaves with other pathways and creates a pattern of dysfunction associated with cardiac muscle. This sets treatments targeting the cGAS-STING pathway apart from traditional therapeutics for cardiomyopathy and achieves better clinical value.

The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases.

Exosomes, mainly derived from mesenchymal stem cells, provide a good reference for cardiac function repair and clinical application in cardiac and vascular diseases by regulating cardiomyocyte viability, inflammatory levels, angiogenesis, and ventricular remodeling after a heart injury. This review presents the cardioprotective efficacy of mesenchymal stem cell-originated exosomes and explores the underlying molecular mechanisms. Furthermore, we expound on several efficient approaches to transporting exosomes into the heart in clinical application and comment on the advantages and disadvantages of each method.

The Chains of Ferroptosis Interact in the Whole Progression of Atherosclerosis.

Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Diabetic Kidney Disease in Rats by Inhibiting Apoptosis and Inflammation.

BACKGROUND AND AIMS: Previous studies have confirmed the anti-inflammation effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo). We aimed to investigate the therapeutic effect of BMSC-Exo on diabetic kidney disease (DKD), as well as the underlying mechanisms. METHODS: SD rats were induced by streptozotocin combined with a high-fat diet to establish a diabetes disease model. BMSCs-Exo were injected via tail veins at a weekly dose of 100 µg for 12 weeks. Pathological changes in the rat kidneys were evaluated using HE, Masson, and Periodic Acid-Schiff and immunohistochemical staining. TUNEL staining and western blot were used to evaluate the expression levels of apoptosis-related proteins in the rat kidney cells. The TNF-α level was detected by PCR and NF-κB (p65) by western blotting to examine the inflammatory responses in the renal tissue. RESULTS: BMSCs-Exo significantly alleviated the renal structural damage and the distribution of apoptotic cells in diabetic rats. Furthermore, BMSCs-Exo increased the expression of pro-apoptosis protein Bax and decreased the expression of apoptosis-executing protein Cleaved Caspase 9 and Cleaved caspase 3. In addition, the transcription level of TNF-α in kidney tissue and NF-κB (p65) expression was also decreased through BMSCs-Exo treatment. Besides, the levels of glucose (GLU), creatinine (Cr), and burea nitrogen (BUN) in diabetic rats were decreased by the BMSC-Exo treatment. CONCLUSIONS: BMSCs-Exo may alleviate diabetic kidney damage by inhibiting apoptosis and inflammation.

cGAS-STING Pathway Performance in the Vulnerable Atherosclerotic Plaque.

The important role of Ca2+ in pathogenic store-operated calcium entry (SOCE) is well-established. Among the proteins involved in the calcium signaling pathway, Stromal interacting molecule 1 (STIM1) is a critical endoplasmic reticulum transmembrane protein. STIM1 is activated by the depletion of calcium stores and then binds to another calcium protein, Orai1, to form a channel through which the extracellular Ca2+ can enter the cytoplasm to replenish the calcium store. Multiple studies have shown that increased STIM1 facilitates the aberrant proliferation and apoptosis of vascular smooth cells (VSMC) and macrophages which can promote the formation of rupture-prone plaque. Together with regulating the cytosolic Ca2+ concentration, STIM1 also activates STING through altered intracellular Ca2+ concentration, a critical pro-inflammatory molecule. The cGAS-STING pathway is linked with cellular proliferation and phenotypic conversion of VSMC and enhances the progression of atherosclerosis plaque. In summary, we conclude that STIM1/cGAS-STING is involved in the progression of AS and plaque vulnerability.

Comparison of successful versus failed percutaneous coronary intervention in patients with chronic total occlusion: A systematic review and meta-analysis.

BACKGROUND: The optimal treatment strategy of chronic total occlusion (CTO) is currently debated. This meta-analysis aimed to evaluate the long-term clinical outcomes of successful percutaneous coronary intervention (PCI) of CTO. METHODS: Electronic databases were searched for studies comparing long-term outcomes between successful PCI in patients with CTO using drug-eluting stents and failed procedures. Meta-analysis was conducted with major adverse cardiac events (MACE) and all-cause mortality during the longest follow-up as endpoints. The combined hazard ratios (HRs) were applied to assess the correlation between successful CTO PCI and MACE/all-cause mortality. RESULTS: Eight studies consisting of 6,211 patients published between 2012 and 2020 met our inclusion criteria, and the CTO PCI success rate was 81.2%. Patients in the failed group were much older, and more likely to have morbidities (hypertension and prior myocardial infarction), reduced left ventricular ejection fraction, and severe lesion characteristics (multivessel disease and moderate/severe calcification). Pooled results indicated that successful CTO PCI was significantly associated with prognosis. Compared to failed recanalization, patients receiving successful procedures had an improved MACE (HR: 0.50, 95% CI: 0.40-0.61, p < 0.001). Subgroup analyses further revealed the prognostic value of successful CTO PCI. However, no difference was observed regarding all-cause mortality (HR: 0.79, 95% CI: 0.61-1.02, p = 0.074). CONCLUSIONS: The present study showed that CTO recanalization was associated with improved long-term outcomes. However, randomized trials are needed to confirm the results due to the mismatch of baseline characteristics.

Revascularization or medical therapy for stable coronary artery disease patients with different degrees of ischemia: a systematic review and meta-analysis of the role of myocardial perfusion.

OBJECTIVE: This study explored the best treatment strategies for stable coronary artery disease (SCAD) patients with differing levels of ischemic severity. METHODS: We conducted a comprehensive search of the PubMed, EMBASE, and Cochrane databases - searching for relevant articles through 4 February 2021. We selected studies comparing different treatments for patients with SCAD who had received ischemia assessments. The primary outcome was death. The secondary outcomes were major adverse cardiovascular events (MACEs) and myocardial infarction (MI). RESULTS: A total of 11 studies, including 35,607 subjects, were selected for this meta-analysis. Results showed that, compared with medical therapy, revascularization could reduce MACE incidence (odds ratio (OR) 0.73, 95% confidence interval (CI): 0.57-0.94, p < 0.05) in SCAD patients with myocardial ischemia, but that it was not effective for patients without ischemia. For mild ischemia, the incidence of death (OR 0.78, 95% CI: 0.59-1.01, p = 0.063), MACE (OR 0.91, 95% CI: 0.48-1.70, p = 0.762), or MI (OR 1.44, 95% CI: 0.94-2.19, p = 0.093) was the same whether they were treated with revascularization or medical therapy. For moderate to severe ischemia, revascularization reduced the incidence of MACE (OR 0.59, 95% CI: 0.42-0.83, p < 0.05) and MI (OR 0.83, 95% CI: 0.71-0.98, p < 0.05), but the incidence of death (OR 0.73, 95% CI: 0.47-1.12, p = .145) was similar. For SCAD patients with severe ischemia, revascularization may confer survival benefits (OR 0.46, 95% CI: 0.21-1.00, p = 0.05). CONCLUSION: For SCAD patients with moderate to severe ischemia, revascularization reduces the MACE and MI incidences, but does not change the incidence of death. Evaluation for myocardial ischemia is vital when selecting a therapeutic strategy.

Quantification of strain analysis and late gadolinium enhancement in coronary chronic total occlusion: a cardiovascular magnetic resonance imaging follow-up study.

BACKGROUND: The present study aimed to investigate the benefits of percutaneous coronary intervention (PCI) in patients with chronic total occlusions (CTOs) by using cardiac magnetic resonance imaging (CMR) feature tracking. METHODS: Fifty-five CTOs with successful CTO-PCI underwent CMR at baseline and 12 months. Feature tracking was applied to measure left ventricle strain index in CTOs with decreased and preserved left ventricular ejection fraction (LVEF). CTOs were also divided into two groups according to the infarct size of 10% or combined with multi-vessel disease. We also measured these parameters in 40 healthy subjects. RESULTS: Three quarters of CTOs showed preserved ejection fraction and no enlargement of left ventricle at baseline, but the global strains were lower than the controls (all P<0.01). In the entire CTO population, left ventricular ejection fraction did not show significant improvement in the 1-year follow-up (59.8%±11.3% vs. 62.0%±8.6%, P=0.08). However, global strains improved over time, and peak global radial strain and circumferential strain showed significant treatment effect of CTO-PCI in the entire CTO population (31.1%±9.9% vs. 34.3%±8.7%, P<0.01; -17.9±3.6 vs. -19.2±3.1, P<0.01), and the subgroup with decreased LVEF, infarct size less than 10%, or multi-vessel disease, but not with the 1-vessel disease. In the LAD and LCX CTO territory, radial and circumferential strain showed treatment effect of CTO-PCI on the recovery of strain parameters (P<0.01 for both). In the RCA CTO territory, circumferential and longitudinal strain showed treatment effect of CTO-PCI on the recovery of strain parameters (P<0.05 for both). CONCLUSIONS: In this single center study, global radial strain and circumferential strain showed treatment effect of successful CTO-PCI at 1-year follow-up in CTOs with the decreased LVEF, infarct size less than 10%, or multi-vessel disease, and the regional strain also showed a similar trend. However, the benefit of CTO-PCI on the strain recovery was not shown in patients with 1-vessel disease. Therefore, whether patients with CTO benefit from PCI still needs further verification.

TLR4-Myd88 pathway upregulated caveolin-1 expression contributes to coronary artery spasm.

AIM: To study the role of toll-like receptors 4-myeloid differentiation factor 88 (TLR4-Myd88) dependent caveolin-1 (Cav-1) expression modulation in coronary artery spasm (CAS) and explore the underlying pathogenic mechanisms. METHODS AND RESULTS: Lipopolysaccharide (LPS) and acetylcholine (Ach) were used to develop the in vitro and in vivo models mimicking the physiological CAS microenvironment. LPS-induced upregulation of Cav-1 expression in mouse coronary and aorta endothelial cells was shown by western blot and immunofluorescence (IF) staining (p < 0.01). Caveolin-1-knockout (Cav-1-/-) mice had reduced aortic inflammation after LPS challenge, and fewer ST segment changes were observed through electrocardiogram (ECG) monitoring compared to wild type mice after LPS and ACh administration. In vitro, pretreating human umbilical vein endothelial cells (HUVECs) with siCav-1 to knock down Cav-1 expression reduced the endothelial inflammation following LPS challenge. SiCav-1 also partially reversed the attenuated Ca2+ concentration after LPS and ACh administration compared to the control group, which was evaluated by fluorescent molecular probing for Ca2+ alternation monitoring (p < 0.05). TLR4 and Myd88 downregulation by siRNA partially blocked the increased Cav-1 mRNA and protein expressions following LPS treatment, as well as partially reversed the decreased NO production evaluated by nitrate reductase method and the impaired Ca2+ concentration of endothelial cells induced by LPS and ACh. CONCLUSION: These findings suggested that Cav-1, which was upregulated by TLR4-Myd88, served as an important modulator of CAS microenvironment establishment in vivo and in vitro, making it a potential pharmacologic target for the treatment of vasospasm via reduced endothelial cell inflammation.