Clinical value of the platelet and inflammatory factor activation in vascular endothelial injury in essential hypertension.

OBJECTIVE: To investigate the clinical value of platelet and inflammatory factor activation in vascular endothelial injury in hypertension. METHODS: A total of 120 hypertension patients diagnosed in our hospital from December 2019 to June 2021 were enrolled as study objects (Hypertension group); besides, another cohort of 60 healthy people undergoing physical examination at the same period were recruited as the controls (Control group). Next, the baseline clinical characteristics of subjects in the two groups were recorded and compared. Specifically, a hematology analyzer was adopt for detecting the mean platelet volume (MPV), platelet distribution width (PDW) and platelet hematocrit (PCT); ELISA for the level of IL-6, IL-8 and TNF-α; PHILIPS EPIQ 7 C (a device assessing endothelial vasodilator function in a non-invasive fashion) for reactive hyperemia index (RHI); univariate and multivariate regression analysis for risk factors triggering endothelial dysfunction; and Spearman correlation analysis for the correlation of platelet activation indicators and inflammatory factor level with vascular endothelial function. RESULTS: Compared with the Control group, the patients in the Hypertension group exhibited higher levels of MPV, PDW, PCT, inflammatory factors (IL-6, IL-8 and TNF-α) and lower RHI. Moreover, Spearman correlation analysis showed a significant negative correlation of MPV, PDW, PCT, IL-6, IL-8 and TNF-α level with RHI level. In addition, univariate and multivariate regression analysis presented that MPV, PCT, IL-8 and TNF-α were risk factors for vascular endothelial dysfunction. CONCLUSION: The activation of platelet and inflammatory factor is closely related to vascular endothelial function injury in patients with hypertension. To be specifically, platelet and inflammatory factor activation can effectively reflect the vascular endothelial function injury in patients with hypertension and has high clinical value.

Connexin 37 Regulates the Kv1.3 Pathway and Promotes the Development of Atherosclerosis.

Objective: To investigate the mechanism of Connexin 37 (Cx37) and Kv1.3 pathways in atherosclerosis (AS). Methods: ApoE-/- mice were given a high-fat diet to establish atherosclerosis (AS) model, and macrophages in mice were isolated and extracted to transfect Cx37 vectors with silencing or overexpressing, and Kv1.3 pathway blockers were used to inhibit the pathway activity. The indexes of body weight, blood glucose, and blood lipid of mice were collected. The protein and mRNA expression levels of Cx37 and Kv1.3 were detected by reverse transcription-PCR (RT-PCR), Western blot, and immunofluorescence technique. Oil red O staining was used to observe plaque area. Masson staining was used to detect collagen content. The concentrations of chemokine CCL7 were quantified using the ELISA kits. CCK8 was used to detect cell proliferation. Results: Cx37 and Kv1.3 were highly expressed in macrophages of AS mice, and the expression of Kv1.3 and CCL7 decreased after Cx37 was silenced, and the proliferation of macrophages was also decreased. Wild-type mice and AS model mice were treated with Cx37 overexpression vectors and Kv1.3 pathway blocking, and it was found that Cx37 overexpression could improve the blood lipid and blood glucose levels and increase the area of AS in AS mice. However, blocking the activity of Kv1.3 pathway can reduce the levels of blood lipid and blood glucose, increase the body weight of mice, and reduce the area of AS mice. Blocking the activity of Kv1.3 pathway can slow down the plaque development of AS mice and make its indexes close to wild-type mice. And the use of Kv1.3 pathway blockers on the basis of overexpression of Cx37 indicated that inhibition of Kv1.3 pathway activity did not affect the expression of Cx37, but could inhibit the collagen content in the plaque area of AS mice, inhibit the expression of chemokine CCL7, and reverse the effect of Cx37 overexpression. Conclusion: Cx37 can improve the activity of macrophages by regulating the expression of chemokines and the activity of Kv1.3 pathway in AS mice, and enrich macrophages in inflammatory tissues and expand the area of plaque formation.

Decreased Mortality with Beta-Blocker Therapy in HFpEF Patients Associated with Atrial Fibrillation.

BACKGROUND: There are no proven effective treatments that can reduce the mortality in heart failure with preserved ejection fraction (HFpEF), probably due to its heterogeneous nature which will weaken the effect of therapy in clinical studies. We evaluated the effect of beta-blocker treatment in HFpEF patients associated with atrial fibrillation (AF), which is a homogeneous syndrome and has seldom been discussed. METHODS: This retrospective cohort study screened 955 patients diagnosed with AF and HFpEF. Patients with a range of underlying heart diseases or severe comorbidities were excluded; 191 patients were included and classified as with or without beta-blocker treatment at baseline. The primary outcome was all-cause mortality and rehospitalization due to heart failure. Kaplan-Meier curves and multivariable Cox proportional-hazards models were used to evaluate the differences in outcomes. RESULTS: The mean follow-up was 49 months. After adjustment for multiple clinical risk factors and biomarkers for prognosis in heart failure, patients with beta-blocker treatment were associated with significantly lower all-cause mortality (hazard ratio (HR) = 0.405, 95% confidence interval (CI) = 0.233-0.701, p=0.001) compared with those without beta-blocker treatment. However, the risk of rehospitalization due to heart failure was increased in the beta-blocker treatment group (HR = 1.740, 95% CI = 1.085-2.789, p=0.022). There was no significant difference in all-cause rehospitalization between the two groups (HR = 1.137, 95% CI = 0.803-1.610, p=0.470). CONCLUSIONS: In HFpEF patients associated with AF, beta-blocker treatment is associated with significantly lower all-cause mortality, but it increased the risk of rehospitalization due to heart failure.

[ARMS-PCR method for detecting multiple NPM1 mutations].

This study was aimed to establish a simple, sensitive detection method for multiple NPM1 mutations, so as to reduce the omission ratio of NMP1 mutant detection. Recombinant plasmids containing wide-type NPM1 and the most common mutations (A, B, C, D) were constructed as the detection objects. The ARMS-PCR for detecting multiple NPM1 mutations was established through designing a pair of specific primers whose 3' end base matched with four mutants (A,B,C,D), but did not matched with wild type NPM1 according to the different base sequence of NPM1 mutants. The feasibility of the ARMS-PCR method was evaluated by assessing the detection range and the sensitivity and comparing with direct sequencing. The results showed that the recombinant plasmids were constructed successfully by restriction analysis and DNA sequencing. The four mutants but not wild type NPM1 were detected by using ARMS-PCR, the detection range of the method was 10(3) copies/ml -10(9) copies/ml and the sensitivity was 0.01%, while the direct sequencing method could not detect the mutations if mutation was less than 10%. It is concluded that the high sensitive ARMS-PCR is established for detecting the four mutations of NPM1 and more than 95% mutants can be detected by this method, providing a new detection method for clinical NPM1 gene mutant.

A new hydrodynamic approach by infusion of drag-reducing polymers to improve left ventricular function in rats with myocardial infarction.

BACKGROUND: Recent studies have shown that drag-reducing polymers (DRPs) prolonged survival time in rats with acute myocardial infarction (MI), but their effect on cardiac function post MI remains unknown. This study sought to test the hypothesis that intravenous infusion of DRPs may improve left ventricular (LV) function in rats following surgically induced MI. METHODS: MI was induced by ligation of the left anterior descending coronary artery in 36 Sprague-Dawley rats, and sham operations were performed in 12 animals. DRPs were then administered to 18 of the MI rats. Echocardiograpy was used to evaluate the changes of impaired LV function and global wall motion. Besides, the hydrodynamic effect of DRPs on microcirculation was also assessed. RESULTS: The survival rate at 24h following MI was significantly different among the sham, MI and DRP groups (p = 0.023). DRP-treated animals had marked smaller left ventricular end-systolic diameter and better anterior systolic wall thickness comparison with untreated rats. Significant improvement of fractional shortening and ejection fraction were detected in MI rats with DRP. Wall motion score index and contrast score index were both significantly reduced by DRP treatment. DRPs were shown to have beneficial effects on microvascular variables including red blood cell velocity, diameter, blood flow and calculated wall shear stress in third-order arteriole. CONCLUSIONS: Acute administration of DRPs improved LV function in a rat model of MI possibly by improving microvascular blood flow due to their unique hydrodynamic properties. DRPs may offer a new approach to the treatment of coronary artery ischemic diseases.

[Protective effects of estrogen on mitochondria in human umbilical vascular endothelial cells].

OBJECTIVE: To investigate the protective effects of estrogen on the mitochondria in human umbilical vascular endothelial cells (HUVECs). METHODS: HUVECs were exposed to H2O2 at 250 micromol/L for 4 h with or without pretreatment with 17-estradiol (E2) and ICI182780. Complex IV activity of the cells was measured with chromometry, and 2, 7-dichlorofluorescein diacetate (DCFH-DA) was used to determine intracellular reactive oxygen species (ROS). Intracellular adenosine triphosphate (ATP) level was quantified with a luciferin- and luciferase-based assay. RESULTS: Compared to the blank control group, H2O2 caused a decrease in complex IV activity, intracellular ATP level, and the cell viability, but elevated intracellular ROS. E2 pretreatment of cells significantly attenuated these effects of H2O2 exposure. ICI182780 administered prior to E2 pretreatment antagonized the protective effects of E2 against H2O2 exposure. CONCLUSION: E2 offers mitochondrial protective effects on HUVECs, which is mediated by the estrogen receptors.

[Relationship between dehydroepiandrosterone and arteriosclerosis in premenopausal and postmenopausal women].

OBJECTIVE: To investigate the correlation between dehydroepiandrosterone and arteriosclerosis in premenopausal and postmenopausal women. METHODS: Forty premenopausal and 40 postmenopausal women were examined for serum concentrations of dehydroepiandrosterone and intima-media thickness of the carotid artery, and the serum concentrations of lipids, estrogen, endothelin, and E-selectin were also measured. RESULTS: Compared with premenopausal women, the mean intima-media thickness was increased but dehydroepiandrosterone and estrogen levels were decreased in postmenopausal women. A significant inverse correlation was detected between the intima-media thicknesses and dehydroepiandrosterone level. The postmenopausal women had decreased antioxidation and elevated low-density lipoprotein level. CONCLUSION: Arteriosclerosis is more likely to occur in women with low dehydroepiandrosterone level which causes decreased antioxidation and elevation of blood lipid levels.