2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration.

Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus angiotensin II- (AngII-) induced AAA formation and to assess the underlying molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII-induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP-9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation, normal T-cells expressed and secreted (RANTES) was significantly upregulated in aortic aneurysm lesions but inhibited by SP600125. In vitro, nicotine induced the expression of MCP-1 and RANTES in both RAW264.7 (mouse macrophage) and MOVAS (mouse vascular smooth muscle) cells in a dose-dependent manner; expression was upregulated by 0.5 ng/mL nicotine but strongly downregulated by 500 ng/mL nicotine. SP600125 attenuated the upregulation of MCP-1 and RANTES expression and subsequent macrophage migration. In conclusion, SP600125 attenuates nicotine plus AngII-induced AAA formation likely by inhibiting MMP-2, MMP-9, MCP-1, and RANTES. The expression of chemokines in MOVAS cells induced by nicotine has an effect on RAW264.7 migration, which is likely to contribute to the development of nicotine-related AAA.

Nicotine-induced upregulation of VCAM-1, MMP-2, and MMP-9 through the α7-nAChR-JNK pathway in RAW264.7 and MOVAS cells.

The ability of nicotine to induce aortic aneurysms has been shown in animal models; however, its underlying mechanisms remain elusive. In the present experiment, both the RAW264.7 and MOVAS cell lines were employed to examine the nicotine-induced modulation of VCAM-1, MMP-2, and MMP-9 expressions in macrophages and vascular smooth muscle cells. Our results showed that nicotine concentrations of both 0.5 and 5 ng/ml induced VCAM-1, MMP-2, and MMP-9 upregulation, while a concentration of 50 ng/ml had a slight inhibitory effect and a concentration of 500 ng/ml showed a significant inhibitory effect. When cells were pretreated with either SP600125 (JNK inhibitor) or PNU-282987 (α7-nAChR agonist) prior to nicotine exposure, the nicotine-induced upregulation of VCAM-1, MMP-2, MMP-9, and p-JNK was suppressed, with a joint treatment producing a more significant inhibitory effect. Moreover, PNU-282987 had a comparable inhibitory effect on VCAM-1, MMP-2, and MMP-9 expressions and JNK activation via phosphorylation as did SP600125. In conclusion, nicotine-induced VCAM-1, MMP-2, and MMP-9 expressions occur in a dose-dependent fashion in both of the cell lines tested. Furthermore, the nicotine exposure equivalent to plasma levels found in regular smokers can augment VCAM-1, MMP-2, and MMP-9 expressions through the α7-nAChR-JNK pathway.

Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin.

Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling in vascular smooth muscle cells, thus preventing excess ECM production, in our already established 3D co-culture vessel models. Our 3D co-culture vessel model, which mimics true blood vessels, is composed of vascular endothelial cells, vascular smooth muscle cells and collagen type I. We validated the profibrogenic effects of leptin and analysed matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase 1 (TIMP1) and collagen types II/IV secretion in 3D vessel models. The protective/inhibitory effects of adiponectin were re-analysed by inhibiting adiponectin receptor 1 (AdipoR) and AdipoR2 expression in endothelial cells using RNAi technology. In the 3D vessel models, adiponectin blocked the leptin-stimulated secretion of collagen types II/IV and TIMP1 while significantly increasing MMP2/9 activity. In endothelial cells, adiponectin induced phosphorylation of AMPK, thereby suppressing leptin-mediated STAT3 phosphorylation through induction of SOCS3 in smooth muscle cells. Our findings indicate that adiponectin disrupted the leptin-induced vascular ECM remodelling via AdipoR1 and enhanced AMPK signalling in endothelial cells, which, in turn, promoted SOCS3 up-regulation in smooth muscle cells to repress leptin-stimulated phosphorylation of STAT3.

Efficacy and safety of a fixed combination of irbesartan/hydrochlorothiazide in Chinese patients with moderate to severe hypertension.

BACKGROUND AND OBJECTIVES: In a multi-center, single-arm, prospective study, we investigated the efficacy and safety of the fixed irbesartan/hydrochlorothiazide combination in Chinese patients with moderate to severe hypertension. METHODS: Eligible patients were aged 18-75 years, with a blood pressure of 160-199 mmHg systolic or 100-119 mmHg diastolic during a 1-week wash-out phase off antihypertensive medication. The enrolled patients started antihypertensive treatment with irbesartan/hydrochlorothiazide 150 mg/12.5 mg once daily, with the possible addition of irbesartan 150 mg once daily and up-titration to irbesartan/hydrochlorothiazide 300 mg/25 mg once daily at 4 and 8 weeks of follow-up, respectively. The primary efficacy variable was the goal blood pressure-attaining rate at 12 weeks of follow-up (<140/90 mmHg, or <130/80 mmHg in patients with diabetes mellitus). RESULTS: In the intention-to-treat analysis (n = 501) at 12 weeks of follow-up, the goal blood pressure-attaining rate was 57.3%, and the mean change in blood pressure from baseline was 27.8 mmHg [95% confidence interval (CI) 26.4-29.1 mmHg; p < 0.001] systolic and 13.5 mmHg (95% CI 12.6-14.4 mmHg; p < 0.001) diastolic. Similar findings were observed in the per-protocol analysis (n = 449). The prevalence of microalbuminuria and left ventricular hypertrophy significantly (p ≤ 0.01) decreased from 33.4% (150/449) and 50.4% (215/427) at baseline to 23.4% (105/447) and 41.3% (176/427) at the end of follow-up, respectively. Four patients (2.0%) reported a serious adverse event. CONCLUSION: The fixed irbesartan/hydrochlorothiazide combination may control blood pressure to the target level in about 60% of Chinese patients with moderate to severe hypertension, with an acceptable safety profile.

Pathogenesis of abdominal aortic aneurysms: role of nicotine and nicotinic acetylcholine receptors.

Inflammation, proteolysis, smooth muscle cell apoptosis, and angiogenesis have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs), although the well-defined initiating mechanism is not fully understood. Matrix metalloproteinases (MMPs) such as MMP-2 and -9 and other proteinases degrading elastin and extracellular matrix are the critical pathogenesis of AAAs. Among the risk factors of AAAs, cigarette smoking is an irrefutable one. Cigarette smoke is practically involved in various aspects of the AAA pathogenesis. Nicotine, a major alkaloid in tobacco leaves and a primary component in cigarette smoke, can stimulate the MMPs expression by vascular SMCs, endothelial cells, and inflammatory cells in vascular wall and induce angiogenesis in the aneurysmal tissues. However, for the inflammatory and apoptotic processes in the pathogenesis of AAAs, nicotine seems to be moving in just the opposite direction. Additionally, the effects of nicotine are probably dose dependent or associated with the exposure duration and may be partly exerted by its receptors--nicotinic acetylcholine receptors (nAChRs). In this paper, we will mainly discuss the pathogenesis of AAAs involving inflammation, proteolysis, smooth muscle cell apoptosis and angiogenesis, and the roles of nicotine and nAChRs.

Monocyte chemoattractant protein-1 mediates angiotensin II-induced vascular smooth muscle cell proliferation via SAPK/JNK and ERK1/2.

Abnormal vascular smooth muscle cells proliferation is the pathophysiological basis of cardiovascular diseases, such as hypertension, atherosclerosis, and restenosis after angioplasty. Angiotensin II can induce abnormal proliferation of vascular smooth muscle cells, but the molecular mechanisms of this process remain unclear. Here, we explored the role and molecular mechanism of monocyte chemotactic protein-1, which mediated angiotensin II-induced proliferation of rat aortic smooth muscle cells. 1,000 nM angiotensin II could stimulate rat aortic smooth muscle cells' proliferation by angiotensin II type 1 receptor (AT(1)R). Simultaneously, angiotensin II increased monocyte chemotactic protein-1 expression and secretion in a dose-and time-dependent manner through activation of its receptor AT(1)R. Then, monocyte chemotactic protein-1 contributed to angiotensin II-induced cells proliferation by CCR2. Furthermore, we found that intracellular ERK and JNK signaling molecules were implicated in angiotensin II-stimulated monocyte chemotactic protein-1 expression and proliferation mediated by monocyte chemotactic protein-1. These results contribute to a better understanding effect on angiotensin II-induced proliferation of rat smooth muscle cells.

IL-8 reduces VCAM-1 secretion of smooth muscle cells by increasing p-ERK expression when 3-D co-cultured with vascular endothelial cells.

OBJECTIVE: The goal of this study was to investigate the crosstalk between vascular endothelial cells (ECs) and smooth muscle cells (SMCs) using a three-dimensional (3-D) co-culture model. In addition, the role of IL-8 in this crosstalk was investigated. METHODS: A 3-D co-culture model was constructed using a Transwell chamber system and type I collagen gel. Human umbilical artery smooth muscle cells (HUASMCs) were suspended in the gel and added to the upper compartment of the Transwell. Human umbilical vein endothelial cells (HUVECs) were then grown on the surface of the gel. The growth of HUASMCs was tested with a CFDA SE cell proliferation kit. IL-8 and other bioactive substances were investigated by ELISA and real-time PCR. The alteration of p-ERK expression related to the change in IL-8 levels was also examined by Western blot analysis. RESULTS: The proliferation rate of HUASMCs in the 3-D co-culture model was 0.679 ± 0.057. Secretion and transcription of VEGF, t-PA, NO and VCAM-1 in the 3-D co-culture model were different than in single (2-D) culture. When 3-D co-cultured, IL-8 released by HUVECs was significantly increased (2.35 ± 0.16 fold) (P﹤0.05) and the expression of VCAM-1 from HUASMCs was reduced accordingly (0.55±0.09 fold). In addition, increasing or decreasing the level of IL-8 changed the level of p-ERK and VCAM-1 expression. The reduction of VCAM-1, resulting from increased IL-8, could be blocked by the MEK inhibitor, PD98059. CONCLUSION: Crosstalk between HUVECs and HUASMCs occurred and was probably mediated by IL-8 in this 3-D co-culture model.

Passive cigarette smoking induces inflammatory injury in human arterial walls.

BACKGROUND: Epidemiological studies have shown that both active and passive cigarette smoking increase the risk of atherosclerosis. But very little is known about the biological processes induced by passive cigarette smoking that contribute to atherosclerosis. We observe the expression of a few of biological and inflammatory markers in human arterial walls in vitro which were treated with the second-hand smoke solution (sidestream whole, SSW), and discuss the possible mechanism of inflammatory injury induced by second-hand smoke. METHODS: The biological markers (platelet endothelial cell adhesion molecule-1, PECAM-1; alpha-smooth muscle actin, alpha-SMA; collagen IV, Col IV) and inflammatory markers (vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1; interleukin-8, IL-8) of human aortal wall were tested by immunofluorescence staining. The levels of MCP-1 and IL-8 mRNA expression were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: No distinct difference was observed between SSW and the control group on the expression of biological markers as assessed by the light microscope. But the inflammatory markers VCAM-1, MCP-1 and IL-8 on the subendothelial layer and smooth muscle cell layers, which are near the endothelium of arterial wall, were strongly stained in the SSW group compared with the control group. Their fluorescence intensities in the 1:40 SSW group (VCAM-1: 0.35 +/- 0.04, MCP-1: 0.34 +/- 0.05, IL-8: 0.37 +/- 0.05) and the 1:20 SSW group (VCAM-1: 0.40 +/- 0.04, MCP-1: 0.52 +/- 0.09, IL-8: 0.51 +/- 0.07) were significantly stronger than the control group (VCAM-1: 0.12 +/- 0.04, MCP-1: 0.06 +/- 0.02, IL-8: 0.24 +/- 0.03) by semi-quantitative analysis of immunofluorescence (P < 0.001 vs control). MCP-1 mRNA expression in the 1:40 SSW (0.15 +/- 0.04) and the 1:20 SSW (0.19 +/- 0.06) group was significantly higher than in the control group (0.09 +/- 0.03) (P < 0.05, P < 0.01 vs control); IL-8 mRNA expression in the 1:40 SSW (0.64 +/- 0.12) and 1:20 SSW (0.72 +/- 0.13) groups was also significantly higher than that in the control group (0.49 +/- 0.13) (P < 0.05, P < 0.01 vs control) by RT-PCR. CONCLUSIONS: It is implied that a second-hand smoke solution induces the inflammatory reaction of the arterial wall by release of inflammatory factors even though there is no distinct structural change on the arterial walls under light microscope, indicating that passive cigarette smoking is related to inflammatory injury in human arterial wall and could be closely related to the early inflammatory stage of atherosclerosis.

[Endothelial progenitor cells related gene expression changes before and early after revascularization in patients with acute myocardial infarction].

OBJECTIVE: The purpose of this study was to observe the endothelial progenitor cells (EPCs) related gene expression changes before and early after revascularization in patients with acute myocardial infarction. METHODS: Peripheral blood samples were taken from patients with acute anterior myocardial infarction 6 hours and 7 days after PCI and stenting. Mononuclear cells (MNCs) were isolated by Ficoll-density centrifugation and cultured in M-199 medium. After 14 days culture, attaching cells incorporated DiI-acetylated low-density lipoprotein (EPCs) were collected and RNA was isolated by Trizol for microarray analysis on 24 genes associated with permissibility/vessel tone (angiotensin system: ACE, AGTR-1, AGTR-2; NO system: eNOS; prostacyclin system: COX-2; endothelin system: ET-1, ETA, ETB; superoxide anions system: SOD-1), angiogenesis (adhesion molecule: CDH5; growth factors and receptors: VEGFR1, VEGFR2, VEGF) and endothelial cell activation (adhesion molecules expression: ICAM1, ICAM2, ICAM3, PECAM-1, E-Selectin, L-Selection, VCAM1; change phenotype from antithrombotic to prothrombotic: tPA, uPA, PAI, vWF). VEGFR2, PECAM-1 and VE-cadherin positive cells were identified by flow cytometry. RESULT: Eight gene expressions (AGTR-1, AGTR-2, COX-2, eNOS, ET-1, ETA, VEGF) were significantly downregulated 7 days post PCI compared to pre-PCI (P < 0.05). Flow cytometry results showed that VEGFR2 positive cells were also significantly reduced post PCI than that of before PCI (P < 0.05). CONCLUSION: PCI down-regulated endothelial progenitor cells related gene expressions in patients with acute myocardial infarction.

[Blood pressure changes post liver transplantation in 206 recipients].

OBJECTIVE: To study the blood pressure (BP) changes in the liver transplant recipients. METHODS: A total of 206 patients without preoperation hypertension received liver transplantation in our hospital from February 2001 to July 2005. The BP level and serum immunosuppressant concentration at preoperation and various time points post operation were determined. RESULTS: Compared with the preoperation, the average systolic and diastolic pressure was significantly increased at the 2 week, 1, 2, 4 and 6 months post operation. The mobility of hypertension increased significantly after liver transplantation, with the highest mobility (46.49%) at the 1st month post operation. There was no linear correlation between the immunosuppressant (FK506) concentration and the BP level at any time point. CONCLUSION: There was a high hypertension incidence after liver transplantation. Although the use of immunosuppressive drugs accompanied with the BP increase, there was no linear correlation between the immunosuppressant concentration and the BP level post operation.

[A clinical intervention study among 463 essential hypertensive patients with metabolic syndrome].

OBJECTIVE: To study the role of baseline risk factors in predicting the onset of diabetes among essential hypertensive patients with metabolic syndrome (MS) and to evaluate an ideal therapeutic regime that could reduce the risk factors and risk of onset of diabetes. METHODS: A randomized parallel clinical trial in essential hypertensive patients of grade 1 or 2 was conducted. Two of the three components (1) increased waist circumference and/or BMI; (2) increased triglycerides (TG) and/or decreased high-density lipoprotein cholesterol; (3) impaired glucose tolerance (IGT) were present define the MS. The three intervention therapy groups were: indapamide + fosinopril (I + F, n = 151); atenolol + nitrendipine (A + N, n = 160); atenolol + nitrendipine + metformin (A + N + M, n = 152). Each case was followed-up monthly and the dosage of medicine taken be adjusted according to their BP level. The plasma glucose during fasting and two hours after taking 75 g glucose orally was also measured every six months. The new onset of diabetes was diagnosed according to the criteria. OGTT, insulin release test, lipid analysis, body weight and waist circumference were measured again at the last follow-up. RESULTS: (1) The lowering of BP was similar among the three groups (P > 0.05). 23 new diabetes onsets occurred, being 10 in group I + F and 8 in group A + N and 5 in group A + N + M, respectively (P > 0.05); (2) Proportions of patients' risk factors decreased significantly in group A + N or A + N + M, e.g. the proportions of high TG in each group reduced by 14.7% and 9.3% respectively (P < 0.05), the central fat distribution reduced by 16.7% and 15.9% respectively (P < 0.05) and the IGT reduced by 6.6% and 29.6% respectively (P < 0.05). However no changes were found in group I + F; (3) After 1 year and 5 months' follow-up, the proportions of main risk factors (high TG, central fat distribution and IGT) in the three groups were 91%, 96%, 83% and 90%, 88%, 47%, respectively. The difference of IGT was significant between two groups (P < 0.01) and the proportions of having three risk factors were 70% and 31% in the two groups (P < 0.01); (4) I + F group was better than A + N group in reduction of TG and central fat distribution. And A + N + M group improved in all risk factors. CONCLUSIONS: IGT alone or combined with increased TG plus abdominal obesity are the most important risk factors in predicting a new onset of diabetes among essential hypertensive patients with MS. Metformin in combination with atenolol plus nitrendipine can significantly prevent the onset of diabetes as well as improve patients' metabolic abnormality.