Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model

Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05). Conclusion CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.

Evaluation of metabolic parameters and aortic elasticity in normotensive children with premature adrenarche

Objectives Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to accelerated atherosclerosis, hypertension, type 2 diabetes mellitus (DM), and polycystic ovary syndrome. Methods Seventy-three patients with premature adrenarche were evaluated for metabolic parameters and aortic elasticity to evaluate the susceptibility to atherosclerosis and compared with a control group. The patients were examined in two groups as overweight and nonoverweight, and metabolic and cardiac parameters were also compared among these groups. Strain, distensibility, and stiffness index parameters were used to evaluate aortic elasticity. Results Biochemical parameters and cardiac measurements were not statistically different between patients and controls. They also did not differ between patients with normal weight and overweight groups. Atherogenic index and insulin resistance were closely related and a positive correlation between cholesterol and triglyceride, and ascending aortic stiffness was found. Conclusions The results may suggest that cholesterol and triglyceride-related arterial involvement is more involved in the pathogenesis of arterial stiffness. It can be considered that ‘being overweight’ or ‘having metabolic profile characterized by insulin resistance and dyslipidemia’ are the major coexisting factors influencing the vascular structure, rather than increased androgens and premature adrenarche itself.

CONVENTIONAL ECHOCARDIOGRAPHY, AORTIC ELASTICITY AND LIPID PROFILES IN OBESE VERSUS HEALTHY CHILDREN

Objectives: To compare conventional echocardiography, aortic elasticity and lipid profiles in overweight or obese children with healthy controls. Methodology: This case control study was conducted on 49 obese or overweight children aged 4 to 16 years, equally matched in age and sex of control that were normal regarding body mass index. Echocardiography and aortic elasticity findings measured for both groups and lipid profiles measured for overweight or obese children only. Data analyzed by SPSS 20 considering 0.05 as significant level. Results: Most of the echocardiography findings such as LVDS(P<0.001), LVDD(P<0.001), PWD(P<0.001), IVSS(P<0.001), LVMI(P<0.001), AS(P<0.001), AD(P<0.001) were higher significantly in obese children whereas, FS(P<0.001), FS(P<0.001), AS beta index(P<0.001) and PSEM(P<0.001) were lower compared to healthy. PWD was higher in obese (0.51±0.08 vs 0.46±0.07) compared to healthy children. Among obese or overweight children, aortic diameter in systole (AoS) (p=0.025) was higher in those with high triglyceride level. LVMI changed from those who had LDL >130. Those who had abnormal LDL (>130) had lower value of AOS (p=0.017). Systolic BP was correlated with AD (p=0.007), Diastolic BP with AS beta Index (p=0.006), AoD with AS (p=0.002), with AD (p<0.001), with AS beta Index (p=0.001) and with PSEM (P<0.001) Conclusion: Heart functions were most at risk in obese children. Amongst obese or overweight children, PWD was higher, when all other heart function were similar. LVMI was higher in children with elevated LDL level.

Aortic Elasticity Evaluated by Pulsed Tissue Doppler Imaging of the Ascending Aorta in Different Diseases: A Systematic Review

Several methods have been applied for the evaluation of aortic elasticity. Pulsed tissue Doppler imaging of the ascending aorta is a noninvasive method applied for the evaluation of aortic elasticity in wide variety of diseases which are reviewed in this study. A comprehensive systematic literature search was carried out in November 2019 using the English databases including PubMed, Scopus, Science Direct, and Embase. All references of eligible articles and published reviews on tissue Doppler imaging were searched for relevant publications. Data were extracted according to predefined criteria (including country of study origin, patient population, number of patients in case and control groups, and results of aortic elasticity evaluation in the specific patient groups compared with controls). Two independent reviewers extracted the data, and the results were checked, compared, and edited by the third reviewer. No formal assessment of the statistics of the primary data was made. The results showed that decreased aortic elasticity is not only present in cardiovascular diseases but also can be identified in diseases of other systems that affect cardiovascular system.

Aortic wall elasticity and left ventricular function in hypertensive patients with nonsignificant coronary artery disease

Purpose Hypertension is an important cause of nonischemic heart failure. It is important to identify subclinical left ventricular dysfunction in patients with hypertension in an early stage to lower the risk of progression to more severe illness. The aim of our study was to assess the correlation between indices of left ventricular function and aortic stiffness in patients with hypertension. Methods Our study was a case control study of 42 hypertensive and 40 normotensive patients with nonsignificant coronary artery disease. All the patients underwent echocardiography and left ventricular ejection fraction, global longitudinal strain, post systolic index, pulsed Doppler early transmitral peak flow velocity, early diastolic mitral annular velocity (e′), and aortic elasticity measurements were calculated. Results The hypertensive patients were older (58.47 ± 9.57 vs. 52.94 ± 10.38 years, p = 0.018) and had a higher body mass index (30.09 ± 5.08 vs. 27.48 ± 4.17 kg/m2, p = 0.013) and E/e′ ratio (8.16 ± 1.81 vs. 6.56 ± 1.71, p < 0.001) and a lower e′ velocity (8.25 ± 2.28 vs. 9.52 ± 2.34 cm/s, p = 0.015) than normotensives. They also had a lower aortic distensibility ( p = 0.008) and a higher aortic stiffness index ( p = 0.039) compared with the normotensive group. The hypertensive patients did not show any association between aortic elasticity and stiffness with age or e′ velocity despite significant association in normotensives. Conclusion Hypertension is associated with a high prevalence of diastolic dysfunction, elevated left ventricular filling pressure, and increased arterial stiffness, all of which have significant association with adverse outcomes. The measurements found in the hypertensive patients compared with the normotensive group may be due to several age-independent mechanisms.