Clinical Efficacy of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Coronary Heart Disease Patients with SYNTAX Score ≥33 and Euro Score ≥6: A Single-Center Retrospective Analysis.

OBJECTIVE: To observe clinical efficacy of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary heart disease patients with SYNTAX scores (SS) ≥33 and Euro Scores (ES) ≥6 who are unsuitable for or have declined coronary artery bypass graft (CABG). METHODS: A total of 117 patients with SS ≥33 and Euro Score (ES) ≥6 who were unsuitable for and/or who had declined CABG between Jan 2021 and June 2022 were enrolled in this retrospective analysis. All patients accepted optimal medical therapy and some accepted an FFR-guided PCI procedure. Patients who only underwent optimal medical therapy were divided into the optimal medical therapy group (OMT group) and patients who simultaneously underwent FFR-guided PCI procedure were divided into the PCI group in this retrospective analysis. All patients accepted follow-up for at least 12 months after discharge. RESULTS: SS and ES in the two groups were not statistically different (p > 0.05). Patients with chronic total occlusion accounted for a greater proportion in the PCI subgroup (31.3%, 5/16) than in other subgroups. Eighteen (18.6%, 18/97) cases in the PCI group developed major adverse cardiac and cerebrovascular events (MACCEs). There were 12 (60%, 12/20) cases of MACCEs in the OMT group, which was statistically different from the PCI group (p < 0.05). CONCLUSIONS: Based on optimal medical therapy, FFR-guided PCI can still have clinical benefit to coronary artery disease patients with SS ≥33 who were not suitable for CABG.

microRNA-497 inhibition mitigates myocardial infarction via enhancing wingless/integrated signal pathway in bone marrow mesenchymal stem cells.

OBJECTIVE: High association between microRNA-497 (miR-497) inhibition and the improvement of myocardial infarction (MI) has been proved. Bone marrow mesenchymal stem cells (BMSCs) therapy is regarded as a highly promising approach to MI treatment. We studied the functional role of miR-497 inhibition in the transplantation of BMSCs for MI treatment. METHODS: BMSCs were isolated from 10 to 14 days old male Sprague-Dawley (SD) rats for in vitro and in vivo experiments. First, flow cytometry was used for BMSCs identification. miR-497 antagomir and agomir were transfected into BMSCs, and the migratory capacity was detected by wound healing assay. Protein levels were analyzed by Western blot analysis. Second, rat MI models were constructed and injected with each experimental group BMSCs. Four weeks later, the cellular morphology of cardiomyocyte and infarcted size was observed after histopathologic evaluation (HE) and Masson's trichrome staining. Moreover, WNT3A siRNA (siWNT3A) was used for further investigating the involvement of Wnt/ß-catenin pathway. RESULTS: BMSCs were confirmed to be CD90+ CD45- CD11b/c- cells. The number of rats with wound closure increased more in miR-497 inhibitor group than that in agomir group, the number markedly decreased in agomir group ( P < 0.01). As the miR-497 decreased, the protein levels of WNT3A, matrix metalloproteinase-9 and ß-catenin were notably increased. The injection of BMSCs inhibiting miR-497 repaired almost all infarcted zones. siWNT3A, on the contrary, could decrease the wound closure rate and relative protein levels and inhibit MI treatment. CONCLUSION: miR-497 antagomir contributes to BMSCs transplantation for MI treatment by Wnt/ß-catenin activation, and Wnt/ß-catenin pathway is essential for the functional effects of miR-497 antagomir.

Osteoglycin silencing exerts inhibitory effects on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation in a mouse model of myocarditis.

Osteoglycin (Ogn), a class III SLRP member with multiple glycosylation sites, has been proposed to be engaged in cardiac dysfunction and adverse remodeling in human heart failure following myocardial infarction. However, the underlying mechanism remains to be elucidated. Thus, we sought to define the role of Ogn in regulation of the Wnt pathway on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation (EMT/EndMT) in mice with myocarditis. The pathological changes are observed, while hematoxylin-eosin staining and picric acid Sirius red staining were conducted in successfully constructed myocarditis mouse models. Immunohistochemistry and enzyme-linked immunosorbent assay were adopted to determine Ogn and ß-catenin levels and serum procollagen propeptide concentrations in the mouse myocardial tissues, respectively. Expression of Ogn and Wnt signaling pathway-related factors were measured by reverse transcription quantitative polymerase chain reaction and western blot assay, cell viability by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell cycle distribution and apoptosis by flow cytometry. We saw indicative pathological changes accompanied by many Ogn and ß-catenin positive cells and increased serum procollagen propeptide, in the mouse myocardial tissues. Loss function assays showed reduced levels of Ogn, ß-catenin, LRP6, TGF-ß1, Twist, FSP-1, α-SMA and higher levels of E-cadherin and VE-cadherin, together with decreased proliferation rate, as well as increased apoptosis rate, indicating that the Wnt signaling pathway, proliferation were inhibited while apoptosis was enhanced with upon gene silencing. Coherently, depletion of Ogn inhibits myocardial fibroblasts proliferation and EMT/EndMT while facilitating myocardial fibroblasts apoptosis in myocarditis through the Wnt signaling pathway, thus serving as an intervention target for the molecular treatment of myocarditis.

Association of G+1688A polymorphism of platelet endothelial cell adhesion molecule-1 gene with myocardial infarction in the Chinese Han population.

In order to investigate the association of G+1688A (Ser563Asn) polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with myocardial infarction (MI) in the Chinese Han population, the G+1688A polymorphism in PECAM-1 gene was detected by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method among 502 subjects, including 218 patients with MI and 284 controls. The results showed that there was significant difference in AA frequencies of genotype G+1688A polymorphism between case and control groups (39% vs 24%, P<0.001). A similar trend was observed on the allele frequencies (A/G: 62% vs 49%, P<0.001). Among the subjects with high serum total cholesterol level or high systolic blood pressure level, the variant AA genotype was associated with high risk of MI (adjusted OR, 2.13; 95% CI, 1.08-4.41 and adjusted OR, 2.53; 95%CI, 1.63-3.63). The single nucleotide polymorphism (SNP) at position +1688 in the exon 8 of PECAM-1 gene was associated with MI and the allele A might be a risk factor for MI in the Chinese Han population.

Application of peripheral-blood-derived endothelial progenitor cell for treating ischemia-reperfusion injury and infarction: a preclinical study in rat models.

BACKGROUND: Our aim was to explore the therapeutic effects of peripheral blood-derived endothelial progenitor cells (PB-EPC) in cardiac ischemia-reperfusion infarction models in rats and in in vitro culture systems. METHODS: Rat models of ischemia reperfusion and myocardial infarction were developed using male, Sprague-Dawley rats. Cardiomyocyte and endothelial cell cultures were also established. Therapeutic effects of PB-EPCs were examined in vivo and in vitro in both models. Rats underwent either cardiac ischemia-reperfusion (n = 40) or infarction (n = 56) surgeries and were transplanted with genetically modified EPCs. Treatment efficacy in the ischemia-reperfusion group was measured by infarct size, myocardial contraction velocity, and myeloperoxidase activity after transplantation. Cardiomyocyte survival and endothelial cell apoptosis were investigated in vitro. Vascular growth-associated protein expression and cardiac function were evaluated in the myocardial infarction group by western blot and echocardiography, respectively. RESULTS: Infarct size and myeloperoxidase activity were significantly decreased in the ischemia-reperfusion group, whereas myocardial contractility was significantly increased in the EPC and Tß4 groups compared with that in the control group. In contrast, no differences were found between EPC + shRNA Tß4 and control groups. Rates of cardiomyocyte survival and endothelial cell apoptosis were significantly higher and lower, respectively, in the EPC and Tß4 groups than in the control group, whereas no differences were found between the EPC + shRNA Tß4 and control group. Four weeks after myocardial infarction, cardiac function was significantly better in the EPC group than in the control group. Expressions of PDGF, VEGF, and Flk-1 were significantly higher in EPC group than in control group. CONCLUSIONS: Study findings suggest that PB-EPCs are able to protect cardiomyocytes from ischemia-reperfusion or infarction-induced damage via a Tß4-mediated mechanism. EPCs may also provide protection through increased expression of proteins involved in mediating vascular growth. Autologous peripheral-blood-derived EPCs are readily available for efficient therapeutic use without the concerns of graft rejection.