马曹
阜外华中心血管病医院 心血管内科
OBJECTIVE:MicroRNA (miR) therapeutics is a promising approach to manage coronary artery disease (CAD). Herein, this research was aimed to explore miR-181c-5p-related mechanisms in CAD through regulating SIRT1.METHODS:A CAD mouse model was established by feeding a high-fat diet in 8-week-old ApoE-/- mice. miR-181c-5p, SIRT1, and acetylated p65 levels in mouse myocardial tissues were evaluated by RT-qPCR and Western blot. Hemodynamic parameters included the maximum rising rate of the left ventricular pressure (lv + dp/dtmax) and the time values from the onset of contraction to dp/dtmax (t-dp/dtmax), while hemorheological indices included whole blood viscosity (low shear, middle shear, or high shear), plasma viscosity, hematocrit, and platelet adhesion were measured. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were detected. Mouse pathological changes, degree of fibrosis, and cardiomyocyte apoptosis in myocardial tissues were assessed by HE, Masson, and TUNEL staining, respectively. The targeting relationship between miR-181c-5p and SIRT1 was verified by bioinformatics tools, dual luciferase reporter gene assay, and RNA pull-down assays.RESULTS:In myocardial tissue of CAD mice, miR-181c-5p and acetylated p65 were upregulated while SIRT1 was downregulated. Downregulating miR-181c-5p or upregulating SIRT1 effectively ameliorated CAD by improving hemodynamics and hemorheology and reducing inflammation, pathological changes, degree of fibrosis, and cardiomyocyte apoptosis in myocardial tissues of mice. miR-181c-5p targeted SIRT1, and overexpression of SIRT1 relieved upregulated miR-181c-5p-induced injuries in CAD mice. Regulating miR-181c-5p and SIRT1 affected the acetylation of p65.CONCLUSION:Downregulation of miR-181c-5p may ameliorate myocardial pathological changes and cardiomyocyte apoptosis in CAD by upregulating SIRT1 expression and decreasing acetylated p65 levels.
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese 2023
BACKGROUND:Chronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA.METHODS:The EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT).RESULTS:Among 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. - 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400-523] vs. 420 [330-475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups.CONCLUSIONS:CSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population.TRIAL REGISTRATION:[chictr.org.cn], identifier [ChiCTR2000038649].
BMC medicine 2023
Background:This study explored the efficacy of the "L-sandwich" strategy, which involves the implantation of stents in the main vessel (MV) and shaft of the side branch (SB) with a drug-coated balloon (DCB) applied to the SB ostium, for coronary true bifurcation lesions.Methods and Results:Of 99 patients with true bifurcation lesions, 38 patients underwent the "L-sandwich" strategy (group A), 32 patients underwent a two-stent strategy (group B), and 29 patients underwent a single-stent + DCB strategy (group C). Angiography outcomes (late lumen loss [LLL], minimum lumen diameter [MLD]), and clinical outcomes (major adverse cardiac events [MACEs]) were analyzed. At 6 months, the MLD of the SB ostium in groups A and B were similar (P > 0.05) and group A larger than group C (P < 0.05). The LLL of group B was the largest among the three groups (P < 0.05). The MLD of the SB shaft in groups A and B were larger than in group C (P < 0.05). The LLL of the SB shaft in group C was the lowest (P < 0.05). Two patients in group B received target vessel revascularization at the 6-month followup (P > 0.05), and patients in the other groups had no MACEs.Conclusions:The "L-sandwich" strategy was feasible for the treatment of true coronary bifurcation lesions. It is a simpler procedure with similar acute lumen gain than the two-stent strategy, results in a larger SB lumen than the single-stent + DCB strategy, and it can also be used as a remedy for dissection following the single-stent + DCB strategy.
Journal of interventional cardiology 2023
Myocardial infarction (MI), which is due to cardiac dysfunction, results in morbidity and mortality. Moreover, the cellular activity of transplanted mesenchymal stem cells (MSCs) generally limits their therapeutic efficacy in the treatment of MI. Here, inject able hyaluronic acid-chitosan/β-glycerophosphate (HA-CS/β-GP) hydrogel-loaded MSCs are prepared, after which their effects on the treatment of MI are investigated. The synthesized HA-CS/β-GP hydrogels exhibit swelling ratio, an in vitro degradation value, and a gelatin time of 82.19 ± 4.1, 88.18% ± 2.4%, and 9 s, respectively. Further, rheological studies revealed that the elastic modulus of the HA-CS/β-GP hydrogels is ≥230 Pa, exhibiting large elastic to viscous modulus ratio, which indicates their mechanical strength. Furthermore, the in vitro 3T3 cell and MSC culture studies confirm the good biocompatibility of the HA-CS and HA-CS/β-GP hydrogels. The implantation of the synthesized hydrogels in the mouse MI model considerably improves the therapeutic effect of the MSCs (enhanced cardiac function, reduced cardiomyocyte apoptosis, and increased vascularization) for the first time. The innovative synergistic strategy of combining injectable HA-CS and HA-CS/β-GP hydro gels with MSCs may be suitable for the effective treatment of cardiac morbidity due to MIs.
Macromolecular bioscience 2022
Vascular smooth muscle cell (VSMC) accumulation and endothelial cell dysfunction are associated with pathogenesis of atherosclerosis. Long noncoding RNA taurine up-regulated gene 1 (TUG1) has been reported to play an important role in cardiovascular diseases, including atherosclerosis. However, the regulatory mechanism underlying TUG1 in atherosclerosis is far from understood. VSMC and human umbilical vein endothelial cells (HUVEC) stimulated by oxidized low-density lipoprotein (ox-LDL) were used as cellular model of atherosclerosis. Cell proliferation and apoptosis were detected by CCK-8, flow cytometry and Western blot. The expression levels of TUG1, microRNA (miR)-148b and insulin-like growth factor 2 (IGF2) were measured by quantitative real-time polymerase chain reaction or Western blot. The target association among TUG1, miR-148b and IGF2 was determined by luciferase reporter assay and RNA immunoprecipitation. The expression of TUG1 was increased in ox-LDL-treated VSMC and HUVEC. Silence of TUG1 inhibited proliferation and promoted apoptosis in ox-LDL-treated VSMC but induced proliferation promotion and apoptosis inhibition in HUVEC stimulated by ox-LDL. miR-148b was a target of TUG1 and its knockdown reversed the effect of TUG1 silence on proliferation and apoptosis of VSMC and HUVEC challenged by ox-LDL. IGF2 was a target of miR-148b and miR-148b regulated proliferation and apoptosis in ox-LDL-treated VSMC and HUVEC by targeting IGF2. TUG1 promoted IGF2 protein expression by sponging miR-148b. TUG1 knockdown attenuated ox-LDL-induced injury through regulating proliferation and apoptosis of VSMC and HUVEC by miR-148b/IGF2 axis, providing a novel mechanism for pathogenesis of atherosclerosis.
Life sciences 2020
