Yuxia Zhao

Prevalence of prehypertension and hypertension in a Chinese rural area from 1991 to 2007

Shandong Province is located in the east of China. The province is characterized by robust economic development, with a rural population accounting for 56% of the total population. However, no data are available regarding temporal changes in the prevalence, awareness, treatment and control of hypertension among this population. Three independent cross-sectional surveys were performed in 1991 (n=8359), 2002 (n=18922) and 2007 (n=20167) in the rural area population, aged 35–74 years. The sampling included a survey on blood pressure and associated risk factors. Although the rate of smoking and alcohol consumption decreased significantly from 1991 to 2007, the prevalence of overweight and obesity increased, whereas that of high-strength physical activity decreased remarkably. In 1991, 2002 and 2007, the prevalence of prehypertension was 33.8, 61.5 and 54.6%, respectively. The prevalence of hypertension was 20.4, 24.5 and 30.6%, respectively. Overall, the rate of hypertension awareness, treatment and control showed a steady increase over the 16-year period, although the control rate of hypertension is still far from being satisfactory. In conclusion, among the Chinese rural population, the prevalence of prehypertension and hypertension increased significantly from 1991 to 2007. Public health programs are required to improve this situation in Chinese rural populations.

The Role of Carotid Plaque Vulnerability and Inflammation in the Pathogenesis of Acute Ischemic Stroke

Background:Increasing evidences show that disruption of carotid plaque followed by arterio-arterial thromboembolism is an important mechanism in the generation of ischemic stroke. Inflammatory mechanisms play a key role in transforming structurally vulnerable plaques into functionally unstable ones. The purpose of the present study is to evaluate the roles of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. Methods:Fifty-two patients with acute ischemic stroke affecting the anterior circulation (stroke group) and 44 with asymptomatic carotid stenosis (asymptomatic group) were investigated. Duplex ultrasonography was used to evaluate the characteristics of carotid plaque and grading the degree of carotid stenosis. Plaque echogenicity was assessed as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Plaque surface was classified as smooth, irregular, or ulcerated. All subjects had duplex-determined 50% to 99% carotid stenosis. Serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), soluble CD40 ligand (sCD40L) and high-sensitivity C-reactive protein (hsCRP) were measured. Results:Plaques in the stroke group were echolucent or predominantly echolucent, whereas those of the asymptomatic group were predominantly echogenic or echogenic plaques (P < 0.05). Irregular and ulcerated plaques were frequently found in stroke patients, while smooth plaques were frequently detected in asymptomatic patients (P < 0.05). Serum levels of MMP-9, sCD40L, hsCRP were higher in stroke than in asymptomatic patients. By contrast, serum TIMP-1 levels were significantly higher in the asymptomatic than in the stroke group. Conclusions:The results suggest that inflammation plays a crucial role in carotid plaque vulnerability and, together with carotid plaque morphology, in the pathogenesis of acute ischemic stroke.

Traditional Chinese medication for cardiovascular disease

Traditional Chinese medication (TCM) is increasingly used to treat cardiovascular disease (CVD) in China and some other Asian countries. However, therapeutic efficacy and adverse effects of TCM are difficult to evaluate because few large-scale, randomized controlled trials (RCTs) enrolling patients with CVD have been performed. In this Review, we critically examine the current evidence on the cardiovascular effects of TCM. We reviewed 68 RCTs that included a total of 16,171 patients. The methodological quality of the trials was generally low. Only three reports described adverse cardiovascular events specifically, although in most studies TCM was associated with significant improvements in surrogate end points for hypertension, coronary heart disease, cardiac arrhythmias, and heart failure. The risk of adverse effects was not increased compared with no intervention, placebo, or Western medications. However, whether TCM is effective in reducing the all-cause or cardiovascular mortality in patients with CVD remains unknown and must be tested in large-scale RCTs with adverse cardiovascular events as primary end points.

Anxiolytic effect of music exposure on BDNFMet/Met transgenic mice

Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF(Met/Met) knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF(Met/Met) mice, but not in BDNF(+/)(-), mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF(Met/Met) mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF(+/)(-) mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF(Met) variant.

Effects and mechanisms of PPARα activator fenofibrate on myocardial remodelling in hypertension

Although peroxisome proliferator‐activated receptor α (PPARα) is highly expressed in the heart, the effects of PPARα on cardiac remodelling and the underlying mechanisms are unclear. The present study was undertaken to test the hypothesis that PPARα activator fenofibrate plays a key role in left ventricular hypertrophic remodelling via the formation of c‐fos/c‐jun heterodimers in spontaneous hypertensive rats (SHRs). Twenty‐four male 8‐week‐old SHRs were randomly divided into two groups, one group treated with oral saline (n= 10) and another treated with oral fenofibrate (60 mg.kg−1.d−1, n= 14). Ten same‐aged Wistar–Kyoto (WKY) rats were selected as a normal control group. Using echocardiography, immunohistochemistry, co‐immunoprecipitation, Western blot analysis and real‐time RT‐PCR, we showed that the left ventricular wall thickness and significantly reduced and left ventricular diastolic function improved in SHRs treated with fenofibrate compared with SHRs treated with saline. Similarly, the excessive collagen deposition and the up‐regulation of collagen I, collagen III, c‐fos and c‐jun seen in SHRs receiving saline were significantly attenuated in SHRs receiving fenofibrate. In addition, fenofibrate markedly decreased the expression of AP‐1 and c‐fos/c‐jun heterodimers (P < 0.01). These results demonstrated that PPARα activator fenofibrate may exert a protective effect on cardiac remodelling in SHRs by decreasing the expression of c‐fos and c‐jun and suppressing the formation of c‐fos/c‐jun heterodimers, which may further inhibit transcription of the downstream genes involved in the pathogenesis of left ventricular hypertrophy induced by hypertension.

Aortic adventitial angiogenesis and lymphangiogenesis promote intimal inflammation and hyperplasia

INTRODUCTIONnAdventitial inflammation is known to influence neointimal formation and vascular remodeling. The present study was aimed to clarify the relationship between neointima hyperplasia and adventitial angiogenesis and lymphangiogenesis after balloon-induced aortic endothelial injury.nnnMETHODSnSeventy male Wistar rats were randomly divided into six interventional groups and one control group. The intimal area/medial area ratio (I/M ratio), the adventitial macrophage index, and the number of adventitial microvessels (Ad-MV) and lymphatic vessels (Ad-LV) in the aorta were measured, and the mRNA expressions of VEGF-A, VEGFR-1, VEGF-C, VEGFR-3, PDGF-B, and PDGFR-beta in the aortic wall were quantified by real-time RT-PCR.nnnRESULTSnCompared with the control group, the I/M ratio, macrophage index, Ad-MV, Ad-LV, and the mRNA expressions of VEGF-A, VEGFR-1, VEGF-C, VEGFR-3, PDGF-B, and PDGFR-beta in interventional groups increased significantly after balloon-induced injury. I/M ratio showed significant correlations with Ad-MV and Ad-LV after balloon intervention. Multiple linear regression analysis indicated that Ad-MV and Ad-LV were independent factors of intimal hyperplasia.nnnCONCLUSIONnAdventitial angiogenesis and lymphangiogenesis are induced by intimal inflammation after balloon injury, and these neogenetic vessels in turn promote intimal inflammation and hyperplasia probably via delivery and activation of inflammatory cells.

Traditional Chinese Medicine for Cardiovascular Disease : Evidence and Potential Mechanisms

Traditional Chinese medicine (TCM) has more than 2,000 years of history and has gained widespread clinical applications. However, the explicit role of TCM in preventing and treating cardiovascular disease remains unclear due to a lack of sound scientific evidence. Currently available randomized controlled trials on TCM are flawed, with small sample sizes and diverse outcomes, making it difficult to draw definite conclusions about the actual benefits and harms of TCM. Here, we systematically assessed the efficacy and safety of TCM for cardiovascular disease, as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and potential mechanisms. Results indicate that TCM might be used as a complementary and alternative approach to the primary and secondary prevention of cardiovascular disease. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease.

Gene silencing of TACE enhances plaque stability and improves vascular remodeling in a rabbit model of atherosclerosis

We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis. Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16. TACE gene silencing reduced remodeling index and plaque burden, and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques. In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-β1 together with reduced number of neovessels in the aorta. TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells. In conclusion, gene silencing of TACE enhanced plaque stability and improved vascular positive remodeling. The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-κB and up-regulated TGF-β1 signaling pathways.

Lymphangiogenesis promotes inflammation and neointimal hyperplasia after adventitia removal in the rat carotid artery

Lymphatic vessels exist in adventitia in the atherosclerotic coronary artery and play an important role in the inflammatory and immune response. After adventitia removal, the carotid wall of rat model showed significantly increased ratio of intimal to medial area (I/M ratio), the number of adventitial lymphatic vessels (Ad-LV) and microvessels (Ad-MV), and macrophage index and expression of VEGF-C, VEGFR-3, PDGF-B and PDGFR-beta. The I/M ratio was significantly correlated with Ad-LV and macrophage index but not Ad-MV. These results suggest that adventitial lymphangiogenesis is stimulated by growth factors released by inflammatory cells in vasculature after adventitia removal, and these neogenetic lymph vessels in turn promote intimal inflammation and hyperplasia, probably via delivery and activation of inflammatory cells.

Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice

Cardiac fibrosis is a common pathological process accompanying diabetes mellitus. In this report, we studied the effects of neferine (a major bisbenzylisoquinline alkaloid derived from lotus embryos) on cardiac fibrosis induced by diabetes mellitus, as well as the underlying molecular pathways. In vivo, type 1 diabetes mellitus was induced in mice by administering streptozotocin. Diabetic mice were treated with neferine through oral gavage, and cardiac function was assessed using echocardiography. Total collagen deposition was assessed by Massons trichrome and Picrosirius staining. In vitro, cardiac fibroblasts were cultured in normal or high-glucose medium with or without neferine. Neferine attenuated left ventricular dysfunction and remodeling and reduced collagen deposition in diabetic mice. In vitro, neferine inhibited cardiac fibroblast proliferation, migration, and differentiation into myofibroblasts. In addition, neferine reduced high-glucose-induced collagen production and inhibited TGF-β1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. These results suggest that neferine may have antifibrogenic effects in diabetes-related cardiac fibrosis.