Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (P<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.
Aging ; Angiotensin II ; Animals ; Aorta/physiopathology* ; Blood Pressure/genetics* ; Gene Expression Profiling/methods* ; Gene Ontology ; Hypertension/genetics* ; Male ; Mice, Inbred C57BL ; Reverse Transcriptase Polymerase Chain Reaction

This study aims to explore the effect of aortic sinus diameter on aortic valve opening and closing performance in the case of no obvious disease of aortic valve and annulus and continuous dilation of aortic root. A total of 25 three-dimensional aortic root models with different aortic sinus and root diameters were constructed according to the size of clinical surgical guidance. The valve sinus diameter S is set to 32, 36, 40, 44 and 48 mm, respectively, and the aortic root diameter is set to 26, 27, 28, 29 and 30 mm, respectively. Through the structural mechanics calculation with the finite element software, the maximum stress, valve orifice area, contact force and other parameters of the model are analyzed to evaluate the valve opening and closing performance under the dilated state. The study found that aortic valve stenosis occurs when the = 32 mm, = 26, 27 mm and = 36 mm, = 26 mm. Aortic regurgitation occurs when the = 32, 36 and 40 mm, = 30 mm and = 44, 48 mm, = 29, 30 mm. The other 15 models had normal valve movement. The results showed that the size of the aortic sinus affected the opening and closing performance of the aortic valve. The smaller sinus diameter adapted with the larger root diameter and the larger sinus diameter adapted with the smaller root diameter. When the sinus diameter is 40 mm, the mechanical performance of the valve are good and it can well adapt with the relatively large range of aortic root dilation.
Aorta ; anatomy & histology ; Aortic Valve ; physiology ; Aortic Valve Insufficiency ; physiopathology ; Aortic Valve Stenosis ; physiopathology ; Humans

PURPOSE: Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We investigated the impact of DM on subclinical CV damage by comprehensive screening protocol in ESRD patients. MATERIALS AND METHODS: Echocardiography, coronary computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD patients from the Cardiovascular and Metabolic disease Etiology Research Center-HIgh risk cohort. RESULTS: The DM group (n=38) had higher systolic blood pressure than the non-DM group (n=53), however, other clinical CV risk factors were not different between two groups. Central aortic systolic pressure (148.7±29.8 mm Hg vs. 133.7±27.0 mm Hg, p= 0.014), PWV (12.1±2.7 m/s vs. 9.4±2.1 m/s, p<0.001), and early mitral inflow to early mitral annulus velocity (16.7±6.4 vs. 13.7±5.9, p=0.026) were higher in the DM group. Although the prevalence of coronary artery disease (CAD) was not different between the DM and the non-DM group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group (p=0.01). In multivariate regression analysis, DM was an independent determinant for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD (p=0.046). CONCLUSION: Diabetic ESRD patients have higher central systolic pressure and more advanced arteriosclerosis than the non-DM control group. These findings suggest that screening for subclinical CV damage may be helpful for diabetic ESRD patients.
Aged ; Aorta ; Biomarkers ; Blood Pressure/physiology ; Blood Pressure Monitoring, Ambulatory ; Coronary Artery Disease/diagnostic imaging/*physiopathology ; Diabetes Mellitus/*physiopathology ; Diabetic Nephropathies/physiopathology ; Echocardiography ; Female ; Humans ; Kidney Failure, Chronic/*physiopathology ; Male ; Middle Aged ; Pulse Wave Analysis ; Regression Analysis ; Risk Factors ; Systole/physiology

OBJECTIVETo evaluate the effect of aorta-iliac bypass total thoracoabdominal aorta aneurysm repair to spinal cord function.

METHODSThis was a prospective study. From June 2014 to April 2015, 31 patients underwent total thoracoabdominal aorta aneurysm repair were treated with aorta-iliac bypass technique. There were 23 male and 8 female patients with a mean age of (36±12) years. A 4-branched tetrafurcate graft was used. The aorta-iliac bypass was established, then distal descending aorta was perfused in a retrograde fashion via bypass graft. Thoracic and abdominal aorta were replaced in a staged fashion. Evoked potentials (EP) monitoring was adopted to assess the spinal cord ischemia throughout the procedure. The intraoperative evoked potentials results, clinical outcomes and follow-up results of this technique were evaluated.

RESULTSThe EP wave disappeared after proximal descending aorta clamped and gradually recovered after the patent segmental arteries reattached. Motor evoked potentials disappeared for (56±18) minutes, somatosensory evoked potentials disappeared for (50±19) minutes. The EP wave was restored to normal at the end of operation in all cases. The somatosensory evoked potentials remained unchanged in 2 cases (false negative). One case died after operation. There were acute kidney dysfunction in 3 cases, and pulmonary haemorrhage in 1 case. No spinal cord injure occurred. The median follow-up after operation was 8 months (ranging from 1 to 11 months). There was no delayed neurologic deficit or relative death.

CONCLUSIONSThere is a transient function loss of spinal cord during the aorta-iliac bypass total thoracoabdominal aorta aneurysm repair. But the process is reversible. The technique of the aorta-iliac bypass is practicable.

Adult ; Aorta, Abdominal ; surgery ; Aortic Aneurysm, Abdominal ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Evoked Potentials, Motor ; Evoked Potentials, Somatosensory ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Spinal Cord ; physiopathology ; Vascular Surgical Procedures ; adverse effects

OBJECTIVETo observe the effect of electroacupuncture (EA) stimulation on the expressions of angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), endothelin-1 (ET1), and endothelin A receptor (ETAR) mRNA in spontaneously hypertensive rat (SHR) aorta.

METHODSEighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui (DU 20) and Zusanli (ST 36) acupoint (SHR-AP) group, and an SHR non-acupoint (SHR-NAP) group, with 6 rats in each group. Six Wistar rats were used as a control. Rats in the SHR-AP group were stimulated by DU 20 and ST 36 acupoints, both of which were connected with EA. EA was handled one time every Monday, Wednesday and Friday, for total 24 times (8 weeks). SHRNAP rats were acupointed at a 15°angle flat into 0.5 cm to two points, which were 1 and 2 cm from rail tip separately. EA parameters were the same as the SHR-AP rats. SHR control rats and Wistar rats were fixed without EA. Real-time quantitative polymerase chain reaction (PCR) was used to measure AGT, AT1R, ET1, and ETAR mRNA expression in rat aorta.

RESULTSEA stimulation significantly reduced rat aorta vascular AGT, ET1, ETAR and AT1R mRNA expressions in the SHR-AP and SHR-NAP groups (P <0.01). Among these four genes, AT1R mRNA expression was significantly lower in the SHR-AP than in the SHR-NAP group (P <0.01).

CONCLUSIONEA could reduce the AT1R mRNA expression in SHR-AP rat aorta, indicating a potential mechanism for the hypotensive effects of EA.

Angiotensinogen ; genetics ; metabolism ; Animals ; Aorta ; metabolism ; physiopathology ; Blood Pressure ; Electroacupuncture ; Endothelin-1 ; genetics ; metabolism ; Gene Expression Regulation ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats, Inbred SHR ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Receptor, Endothelin A ; genetics ; metabolism

OBJECTIVETo observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.

METHODSEAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.

RESULTSCompared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).

CONCLUSIONSModel rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.

Animals ; Aorta ; Cell Proliferation ; Disease Models, Animal ; Hypertension ; physiopathology ; I-kappa B Proteins ; Interleukin-6 ; Leptin ; blood ; NF-KappaB Inhibitor alpha ; NF-kappa B ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Wistar ; Suppressor of Cytokine Signaling Proteins ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha

PURPOSE: Despite technical simplicity and the low cost of brachial-ankle pulse wave velocity (BA-PWV), its use has been hampered by a lack of data supporting its usefulness and reliability. The aim of this study was to evaluate the usefulness of BA-PWV to measure aortic stiffness in comparison to using cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: A total of 124 participants without cardiovascular risk factors volunteered for this study. BA-PWV was measured using a vascular testing device. On the same day, using CMR, cross-sectional areas for distensibility and average blood flow were measured at four aortic levels: the ascending, upper thoracic descending, lower thoracic descending, and abdominal aorta. RESULTS: Compared to PWV measured by CMR, BA-PWV values were significantly higher and the differences therein were similar in all age groups (all p<0.001). There was a significant correlation between BA-PWV and PWV by CMR (r=0.697, p<0.001). Both BA-PWV and PWV by CMR were significantly and positively associated with age (r=0.652 and 0.724, p<0.001). The reciprocal of aortic distensibility also demonstrated a statistically significant positive correlation with BA-PWV (r=0.583 to 0.673, all p<0.001). CONCLUSION: BA-PWV was well correlated with central aortic PWV and distensibility, as measured by CMR, regardless of age and sex.
Adult ; Ankle Brachial Index/*methods ; Ankle Joint ; Aorta/anatomy & histology/*physiology ; *Blood Flow Velocity ; Cardiovascular Diseases ; Female ; Heart/physiopathology ; Humans ; *Magnetic Resonance Imaging, Cine ; Male ; Pulse Wave Analysis/*methods ; Regional Blood Flow ; Reproducibility of Results ; Risk Factors ; *Vascular Stiffness

OBJECTIVETo investigate the differences in central hemodynamic indices between hypertensive and normotensive subjects and identify the blood pressure index that the most strongly correlate with arterial stiffness and vascular damage markers.

METHODSA cohort of 820 hypertensive patients and 820 normotensive individuals matched for age and gender were enrolled in this study. We measured carotid-femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and central blood pressures using pulse wave analysis and applanation tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in these subjects.

RESULTSIn both hypertensive and normotensive subjects, the central systolic blood pressure (SBP) and pulse pressure (PP) were significantly lower than brachial SBP and PP; this PP amplification was significantly lower in the normotensives (9.85∓6.55 mmHg) than in the hypertensives (12.64∓6.69 mmHg), but the amplification ratios were comparable between the two groups. Blood pressure and age were closely related with aortic arterial stiffness. Compared with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV and AIx, and showed significantly lowered PP amplification ratio with age. Central PP was more strongly related to arterial stiffness and vascular damage markers than the other pressure indices. Multivariate analyses revealed that carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not by the mean blood pressure or brachial PP.

CONCLUSIONThe central PP is a more direct indicator of central arterial stiffness and a better marker of vascular aging than other blood pressure variables. These findings support the use of central blood pressure as a treatment target in future trials.

Aorta ; physiopathology ; Arterial Pressure ; Blood Pressure ; Case-Control Studies ; Hemodynamics ; Humans ; Hypertension ; Pulse Wave Analysis ; Vascular Stiffness

OBJECTIVESTo investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms.

METHODSThirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups (8 in each group): model group (placebo), positive control group (27 mg/kg of Captopril Tablets), Sapindus saponins groups (27 mg/kg and 108 mg/kg, respectively). Another 8 healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter (BP-6). Furthermore, the contents of angiotensin II (Ang II) in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA), the gene expression of receptor angiotensin type 1 (AT1R) in aorta was determined by quantitative realtime polymerase chain reaction (qRT-PCR). The protein expression of transforming growth factor-β1 (TGF-β1) and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) was determined by Western blotting. The contents of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin (HE) or Masson staining.

RESULTSThirty minutes after single or continuous treatment, systolic blood pressure (SBP) was reduced significantly in Sapindus saponins groups. And the contents of AngII, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF-β1 were significantly suppressed dose-dependently (P<0.05 or P<0.01). With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly.

CONCLUSIONSOur findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang II and AT1R.

Angiotensin II ; metabolism ; Animals ; Aorta ; drug effects ; pathology ; physiopathology ; Blood Pressure ; drug effects ; Collagen ; metabolism ; Female ; Hypertension ; blood ; drug therapy ; enzymology ; physiopathology ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Phosphorylation ; drug effects ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Inbred SHR ; Receptor, Angiotensin, Type 1 ; metabolism ; Renin-Angiotensin System ; drug effects ; Sapindus ; chemistry ; Saponins ; pharmacology ; therapeutic use ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; p38 Mitogen-Activated Protein Kinases ; metabolism

Computational fluid dynamics (CFD) technology has the potential to simulate normal or pathologic aortic blood flow changes of mechanical properties and flow field, thereby helping researchers understand and reveal the occurrence, development and prognosis of aortic disease. In aortic diseases research, the initial conditions of CFD numerical simulation has experienced a developed process from idealization (forward engineering), rigid vessel wall, uniform cross-sections, laminar flow and stable blood flow towards personalization (reverse engineering), elastic vessel wall (fluid-solid coupling technique), cone-shaped diminishing cross-sections, turbulent flow, pulsatile blood flow. In this review, the research status, the technical superiority and application prospect of CFD technology were discussed with examples in following three major application areas: (1) dynamics characteristic and mechanical properties in normal thoracic aorta; (2) occurrence, advance and disruptive risk predicting in thoracic aortic aneurysm; (3) therapeutic effect and aneurysmal dilatation simulation in thoracic aortic dissection. For the future, the CFD technology may profoundly put an influence on the awareness to aortic diseases and treatment strategies.
Aorta ; pathology ; physiology ; Aortic Aneurysm, Thoracic ; physiopathology ; Computer Simulation ; Dilatation ; Hemodynamics ; Humans ; Pulsatile Flow ; Regional Blood Flow