Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy.

The activation of mammalian ste20­like kinase1 (Mst1) is a crucial event in cardiac disease development. The inhibition of Mst1 has been recently suggested as a potential therapeutic strategy for the treatment of diabetic cardiomyopathy. However, whether silencing Mst1 also protects against hypertensive (HP) myocardial injury, or the mechanisms through which this protection is conferred are not yet fully understood. The present study aimed to explore the role of Mst1 in HP myocardial injury using in vivo and in vitro hypertension (HP) models. Angiotensin II (Ang II) was used to establish HP mouse and cardiac microvascular endothelial cell (CMEC) models. CRISPR/adenovirus vector transfection was used to silence Mst1 in these models. Using echocardiography, hematoxylin and eosin staining, Masson's trichrome staining, the enzyme­linked immunosorbent assay detection of inflammatory factors, the enzyme immunoassay detection of oxidative stress markers, terminal deoxynucleotidyl transferase dUTP nick­end labeling staining, scanning electron microscopy, transmission electron microscopy, as well as immunofluorescence and western blot analysis of the autophagy markers, p62, microtubule­associated proteins 1A/1B light chain 3B and Beclin­1, it was found that Ang II induced HP myocardial injury with impaired cardiac function, increased the expression of inflammatory factors, and elevated oxidative stress in mice. In addition, it was found that Ang II reduced autophagy, enhanced apoptosis, and disrupted endothelial integrity and mitochondrial membrane potential in cultured CMECs. The silencing of Mst1 in both in vivo and in vitro HP models attenuated the HP myocardial injury. On the whole, these findings suggest that Mst1 is a key contributor to HP myocardial injury through the regulation of cardiomyocyte autophagy.

[Analysis of influencing factors on circadian blood pressure of hypertensive patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the effect of obesity, arousal, hypoxia and sympathetic activation on the circadian blood pressure of hypertensive patients with obstructive sleep apnea-hypopnea syndrome. METHODS: Polysomnography (PSG) was performed in 436 hypertensive patients complaining of snoring, daytime sleepiness, lips cyanosis, hyperhemoglobinemia of unknown etiology, or with refractory hypertension. Hypertensive subjects were divided into four groups according to apnea-hypopnea index (AHI): hypertensive with mild obstructive sleep apnea-hypopnea syndrome (OSAHS) (n = 131), hypertensive with moderate OSAHS (n = 95), hypertensive with severe OSAHS (n = 95) and hypertensive without OSAHS as control group (n = 115). The ambulatory blood pressure monitoring (ABPM), PSG, urine electrolyte, and urine vanillylmandelic acid (VMA) were compared among groups. Factor analysis was employed to identify common factors related to the alterations of circadian blood pressure. Multiple linear regression analysis was used to analyze the influencing factors of the observed variables. RESULTS: There were significant differences among groups in age, neck circumference and waist circumference(P < 0.001). In severe group, 24 hour average systolic blood pressure (24 hSBP)[ (137.0 ± 16.8) mm Hg vs.(131.3 ± 11.9)mm Hg, (131.3 ± 13.2)mm Hg (1 mm Hg = 0.133 kPa)], daytime systolic blood pressure (day-SBP) [(140.8 ± 16.8) mm Hg vs. (135.7 ± 11.9) mm Hg, (135.3 ± 13.5) mm Hg]and night systolic blood pressure (night-SBP)[ (130.9 ± 17.0) mm Hg vs.(124.5 ± 14.0 )mm Hg, (124.3 ± 13.2) mm Hg] were significantly higher than those of control or mild OSAS groups (P < 0.01). Factor analysis showed that body mass (BM), life style, urine electrolyte, age and course of disease (ACD) were the common factors influencing circadian blood pressure. OSAHS was correlated with declining percentage of SBP (ß = -0.128, P < 0.01) and declining percentage of DBP (ß = -0.126, P < 0.01). The contribution according to priority was ACD > OSAHS > BM for declining percentage of SBP (ß = -0.148, P = 0.002;ß = -0.128, P = 0.007;ß = 0.099, P = 0.035), OSAHS > ACD > BM for declining percentage of DBP(ß = -0.126, P = 0.008;ß = -0.105, P = 0.026;ß = 0.097, P = 0.042). CONCLUSION: OSAHS, ACD and BM are the independent risk factors contributing to the alterations of circadian blood pressure in hypertensive patients with obstructive sleep apnea-hypopnea syndrome.

Genetic polymorphism of six transmembrane protein of prostate 2 associated with diabetes mellitus in Xinjiang Uygur population.

OBJECTIVE: To investigate the association between the genetic variations of six transmembrane protein of prostate 2 (STAMP2) with type 2 diabetes mellitus (T2DM) in Xinjiang Uygur population. METHODS: A case-control study was conducted based on epidemiological investigation. A total of 1838 Uygur subjects were selected and divided into two groups: T2DM group (n=274) and control group (n=1564). All exons, flanking introns, and the promoter regions of STAMP2 gene were sequenced in 48 Uygur Xinjiang population with diabetes. Representative variations selected were genotyped by TaqMan-PCR method in all individuals. RESULTS: Ten novel and 6 known variations in the STAMP2 gene were identified. The distribution of genotype rs8122 significantly differed between T2DM group and control group (P=0.05), whereas the distribution of genotypes rs1981529 and rs34741656 showed no such difference. The fasting insulin in the total cohort and homeostasis model of assessment index in females showed significant difference between these two groups (P<0.05), while the adjusted P value showed no statistical significance (P>0.05). In the male population, the different genotypes of rs8122 variation of STAMP2 gene were not significantly different (P>0.05). CONCLUSION: Three polymorphisms (rs8122, rs1981529 and rs34741656) of STAMP2 gene may be not related with T2DM in Xinjiang Uygur population.

[Impact of body mass index on incidence of obstructive sleep apnea-hypopnea syndrome in hospitalized hypertensive patients].

OBJECTIVE: To investigate the impact of obesity on incidence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in hospitalized hypertensive patients. METHODS: A total of 825 hospitalized hypertensive patients from April 1 to June 30 in 2009 in our hospital were included. Patients were asked to answer the questions concerning snoring, daytime sleepiness. Patients with loud snoring and daytime sleepiness, tubbiness neck, retrognathia, enlarged tongue, orolingual cyanosis were selected to undergo polysomnography monitoring for a whole night. OSAHS is defined by clinical symptoms and apnea-hypopnea index (AHI) not less than 5 per hour. RESULTS: (1) The detection rate of OSAHS in this cohort was 23.52% (178/825), 34.34% (148/431) in males and 11.68% (46/394) in females respectively. (2) The detection rate was 6.6% (12/183) in normal weight subjects, 22.22% (78/351) in overweight subjects and 36.75% (104/283) in obesity subjects (χ(2) = 56.736, P < 0.01). The severe OSAHS rate in obesity group (16.61%) was significantly higher than that in normal weight group (2.19%) and overweight group (7.69%, χ(2) = 29.219, P < 0.01). (3) The OSAHS rate was 7.83% (9/115) in normal waist circumference group and 26.29% (184/700) in centricity obesity group (χ(2) = 18.623, P < 0.01). The severe OSAHS rate was 2.61% (3/115) in normal waist circumference group and 10.57% (74/700) in centricity obesity (χ(2) = 7.32, P < 0.01). (4) The moderate to severe OSAHS rate increased in proportion with BMI increase in female patients (χ(2) = 5.846, P < 0.05) and increased in proportion with BMI and waist circumference increase in male patients (P < 0.01). CONCLUSIONS: The incidence of OSAHS in hypertensive patients is high. Obesity further increases the morbidity of OSAHS in hypertensive patients.

[Association between genetic polymorphism of the six-transmembrane protein of prostate 2 and obesity in Uygur].

OBJECTIVE: To investigate the association between genetic variations of the six transmembrane protein of prostate 2 (STAMP2) and obesity in Xinjiang Uygur population. METHODS: A total of 2332 Uygur subjects (1455 obesity and 877 non-obesity control subjects) were included in this case-control study based on epidemiological survey. Genetic variations of STAMP2 gene functional region were sequenced. The representative variations selected were genotyped by TaqMan-PCR method. RESULTS: Twenty genetic variations, including 14 novel variations, were identified. The genotype distributions of the control group and obesity group were in the Hardy-Weinberg equilibrium (both P > 0.05). The frequency of AA of rs1981529 (67.6% vs. 62.8%, P < 0.05) and the frequency of G-A-G haplotype (62.4% vs. 58.9%, P < 0.05) in obesity group were significantly higher than that in controls while the frequency of A-G-G haplotype was significantly lower in the obesity patients than that in the control group (17% vs. 20%, P < 0.05). After adjusting age, sex, smoking and drinking, logistic regression analysis showed that the AA genotype of rs1981529 (OR: 1.276, 95%CI: 1.049 - 1.552; P < 0.05) and the G-A-G haplotype (OR: 1.356, 95%CI: 1.007 - 1.862, P < 0.05) were the independent risk factors for obesity in this cohort. CONCLUSION: The AA genotype of rs1981529 and G-A-G haplotype are associated with obesity in Uygur population of Xinjiang.

[A study of relationship between obstructive sleep apnea-hypopnea syndrome in hypertension and insulin].

OBJECTIVE: To investigate the association between the obstructive sleep apnea-hypopnea syndrome (OSAHS) in hypertension and insulin. METHODS: A total of 521 patients were divided into 4 groups according to apnea-hypopnea index and OSAHS degrees. The control group (group I), mild OSAHS group (group II), moderate OSAHS group (group III) and severe OSAHS group (group IV) had 89 patients, 194 patients, 118 patients and 120 patients respectively. RESULTS: The BMI [(30.4 ± 3.8) kg/m(2)], apnea-hypopnea index (AHI, 3.8 ± 0.1), Fasting insulin (FIns) [(3.08 ± 0.26) mU/L] and insulin resistance (2.43 ± 0.27) of patients in severe OSAHS group were significantly higher than that of in the control, mild OSAHS group and moderate OSAHS group (P < 0.01). The levels of saturation of minimum oxygen from skin of patients in severe OSAHS group was significantly lower (MSpO(2)) than in that of the control, mild OSAHS group and moderate OSAHS group. Multiple linear regression analysis showed that fasting plasma insulin and insulin resistance was positive correlation with apnea-hypopnea index, while they also negatively associated with saturation of minimum oxygen. CONCLUSIONS: FIns and insulin resistance strongly associate with AHI and levels of saturation of minimum oxygen from skin. Hypertensive patients with OSAHS have more chances to suffer with insulin resistance.