Aortic Wall Thickness Research Articles

Abstract 230: Repair of Aortic Coarctation in Neonates Less than Two Kilogram

Objective: Though a significant number of low birth weight and premature neonates are born with aortic coarctation, waiting for the child to grow before intervening rarely permits significant useful weight gain and puts the child at risk of interim complications. Previous studies of early operation on these patients have shown a high hospital mortality up to 25% (25 out of 100) and 30% (30 out of 100) recurrence in one year. We reviewed our data to ascertain whether modern approaches allow better outcomes for these children. Methods: All patients weighing less than 2 kg with isolated coarctation between August 2008 and November 2015 were studied by retrospective chart review to ensure greater than 24 months follow-up. Eleven patients underwent extended end-to side surgical repair. In-hospital and medium term follow-up data were collected. Data are expressed as median (range). Results: Weight at time of surgery was 1.8kg (1.6-1.9). There were no deaths, in-hospital or during follow-up. One patient developed postoperative chylothorax. In-hospital stay was 18 days (4-47). At follow-up of 68 months (28-115) echocardiographic velocity across the repair was 1.6m/sec (1.4-4.5). One patient with William’s syndrome had evidence of recoarctation and required balloon coarctoplasty followed by stenting. This patient had grossly abnormal vessels at the time of initial surgery with aortic wall thickness greater than 3mm. Conclusions: Neonates below 2kg can undergo coarctation repair safely with low incidence of recurrence. Waiting for growth in this cohort of patients cannot therefore be justified.

Heparanase inhibition attenuates atherosclerosis progression and liver steatosis in E0 mice

Background and aimsIncreased oxidative stress is associated with accelerated atherosclerosis. Emerging evidence highlights the role of heparanase in atherogenesis, where heparanase inhibitor PG545 reduces oxidative stress in apolipoprotein E deficient mice (E0 mice). Herein, we studied the effects of PG545 on atherosclerosis progression in E0 mice. MethodsMale E0 mice fed a high-fat diet (n = 20) were divided into 3 groups treated with weekly intraperitoneal injections of either low (0.2 mg/mouse) or high dose (0.4 mg/mouse)PG545 or normal saline (controls) for twelve weeks. Body weight and food intake were measured weekly. At the end of the treatment period, blood pressure was measured, animals were sacrificed and serum samples were collected and assessed for biochemical parameters and oxidative stress. Aortic vessels and livers were collected for atherosclerotic plaques and histopathological analysis, respectively. ResultsBlood pressure decreased in mice treated with low, but not high dose of PG545. In addition, heparanase inhibition caused a dose-dependent reduction in serum oxidative stress, total cholesterol, low-density lipoproteins, triglycerides, high-density lipoproteins, and aryl esterase activity. Although food intake was not reduced by PG545, body weight gain was significantly attenuated in PG545 treated groups. Both doses of PG545 caused a marked reduction in aortic wall thickness and atherosclerosis development, and liver steatosis. Liver enzymes and serum creatinine were not affected by PG545. ConclusionsHeparanase inhibition by PG545 caused a significant reduction in lipid profile and serum oxidative stress along with attenuation of atherosclerosis, aortic wall thickness, and liver steatosis. Moreover, PG545 attenuated weight gain without reducing food intake. Collectively, these findings suggest that heparanase blockade is highly effective in slowing atherosclerosis formation and progression, and decreasing liver steatosis.

Chios mastic gum decreases renin levels and ameliorates vascular remodeling in renovascular hypertensive rats.

Chios mastic gum (CMG) exerts robust anti-inflammatory and antioxidant properties and it affects pathways that are implicated in the pathophysiology of endothelial and vascular inflammation. Aim of this study was to test the hypothesis that CMG administration lowers blood pressure (BP) and improves hypertension-induced target organ damage. 2-kidney, 1-clip (2K1C) hypertensive rats were treated with CMG (40 mg/kg body weight/day) for 2-weeks after the establishment of hypertension. Acute CMG administration lowered systolic, diastolic and mean arterial BP, while these hemodynamic effects were sustained throughout the 2-week administration period. CMG group also exhibited alleviated target organ damage as proposed by amelioration of biomechanical properties of the aorta -including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. The anti-hypertensive effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis indicated that the effect of CMG on organ damage was BP-lowering dependent and was not associated with direct effects of renin or with its anti-inflammatory properties. We suggest a BP lowering effect of CMG via down-regulation of renin excretion associated with attenuation of target organ damage and inflammatory status. These observations provide profound evidence for the beneficial role of CMG in hypertension, which could possibly translate to further clinical research.

Role of activating transcription factor 3 in fructose-induced metabolic syndrome in mice.

Activating transcription factor 3 (ATF3) has been implicated in cardiovascular disease and inflammation. This study examined the effects of ATF3 knockout (KO) on blood pressure, glucose intolerance, dyslipidemia, inflammation, and visceral adiposity in mice fed who did and did not consume a high-fructose diet. Male mice were divided into four groups (N = 15 for each group): the Con (control) group (wild-type mice fed a standard chow diet), Fru group (wild-type mice fed a high-fructose [60% fructose] diet), ATF3KO-Con group (ATF3 KO mice fed a standard chow diet), and ATF3KO-Fru group (ATF3 KO mice fed a high-fructose [60% fructose] diet). Experiments were conducted for 8 weeks. Our data demonstrated that ATF3 KO mice have lower systolic blood pressure (SBP) levels than do wild-type mice, and that high-fructose diets increase SBP levels in both wild-type and ATF3 KO mice. ATF3 KO in mice increased the serum levels of glucose, insulin, triglycerides, tumor necrosis factor-alpha, and intercellular adhesion molecule-1, impaired endothelium-dependent aortic relaxation, increased aorta wall thickness and lipid peroxide, and expanded visceral adiposity. These symptoms resembled those exhibited by the wild-type mice fed a high-fructose diet, which caused hyperglycemia, insulin resistance, dyslipidemia, endothelium-dependent aortic dysfunction, inflammation, aorta remodeling, and visceral adiposity. A high-fructose diet among ATF3 KO mice deteriorated metabolic parameters and inflammatory cytokines. The present results therefore suggest that ATF3 deficiency is involved in the pathogenesis of metabolic syndrome and ATF3 might have a therapeutic role in fructose-induced impairment of endothelium-dependent aortic relaxation, a rising of inflammatory cytokines, and metabolic syndrome.

Porphyromonas gingivalis vesicles reduce MDA-LDL levels and aortic wall thickness in high fat diet induced atherosclerosis rats

BackgroundRecently, atherosclerosis-associated disease has been reported simultaneously increased. Whereas, to date, no atherosclerosis vaccine is available. Since the epitope mimicry between malondialdehyde low-density lipoprotein (MDA-LDL) and arginine specific epitope gingipain (Rgp) on the Porphyromonas gingivalis vesicles has been reported, it raises an opportunity to employ the potency of P. gingivalis as an atherosclerosis vaccine. ObjectiveTo evaluate the potency of P. gingivalis vesicles to prevent atherosclerosis, by assessing MDA-LDL level, visceral fat, body weight, and aortic wall thickness, in rats model. MethodsFive groups of rats (n = 10 per group), three treatment groups, one positive and negative control group were assigned and adapted with high fat diet for 8 weeks. The treatment groups were injected with P. gingivalis vesicles with and without adjuvant with four booster doses. The level of MDA-LDL serum, visceral fat, body weight, and aortic wall thickness were measured in the end of the course. ResultsOur present study found that decreased in MDA-LDL levels (p = 0.037) and aortic wall thickness (p = 0.016) were observed in rats treated with vesicles and adjuvants, but not with vesicles or adjuvants only, compared to negative control. Moreover, MDA-LDL levels in rats immunized with vesicles and adjuvants were significantly lower than healthy rats. However, body weight (p = 0.329 and visceral fat (p = 0.789) were not significantly different in all treatment groups compared to control. ConclusionsImmunization with P. gingivalis vesicles and adjuvants significantly reduces MDA-LDL level and aortic wall thickness in rats model.

ACUTE AND CHRONIC EFFECTS OF CHIOS MASTIC GUM ON BLOOD PRESSURE IN A RODENT MODEL OF 2-KIDNEY 1-CLIP HYPERTENSION

Objective: Chios mastic gum (CMG), a Greek plant resin, has been studied for its protective role against endothelial and vascular inflammation by suppressing oxidative stress and downregulating the expression of pro-inflammatory mediators. Objective: We sought to investigate the effect of CMG administration on blood pressure (BP) and hypertension-induced target organ damage. Design and method: 16-week-old male Wistar rats were allocated into 3 groups: Control group; 2-kidney, 1-clip (2K1C) group; CMG group which was treated with CMG (40 mg/kg body weight /day) for 2-weeks after the establishment of hypertension. Results: Acute CMG administration led to a decrease in systolic, diastolic and mean arterial BP (153 vs 188 mmHg, 108 vs 141 mmHg and 122 vs 156 mmHg for CMG and 2K1C groups, respectively), while these hemodynamic effects were sustained throughout the 2-week administration period (136 vs 194 mmHg, 100 vs 141 mmHg and 112 vs 159 mmHg for CMG and 2K1C groups, respectively. CMG also attenuated target organ damage as proposed by amelioration of biomechanical properties of the aorta –including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. Furthermore, CMG administration was associated with decreased interleukin-6 (IL-6) and C-reactive protein (CRP) levels. The BP lowering effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis showed that the amelioration of organ damage was BP-lowering dependent and was not correlated with direct effects of renin or with its anti-inflammatory properties. Conclusions: Our results indicate an anti-hypertensive effect of CMG via down-regulation of renin excretion and suppression of the inflammatory cascade associated with alleviation of target organ damage. These observations provide substantial evidence for the potentially beneficial role of CMG in treating hypertension, yet clinical translation studies are further required.

Abstract 106: Young Tgfbr2 G357W/+ Mice Have Decreased Expression of TGF-β Ligands and Receptors in the Proximal Aorta, Aortic Root Dilation, and Aortic Elongation

Introduction: Tgfbr2 G357W/+ mice have a loss-of-function Tgfbr2 allele ( G357W ) that is orthologous to an allele found in humans with Loeys-Dietz syndrome (LDS). Tgfbr2 G357W/+ mice have kyphosis, aortic dilation and elongation, and die suddenly from aortic rupture. Elevations of mRNA encoding TGF-β ligands in cultured vascular smooth muscle cells from Tgfbr2 G357W/+ mice and LDS patients—as well as increased expression of Tgfb1 and Col1a1 and elevation of both P-Smad2 and P-ERK1/2 in aortic roots of older (24-36-week) Tgfbr2 G357W/+ mice—suggest that paradoxically increased TGF-β signaling might be responsible for aortic pathology in LDS. Hypothesis: We hypothesized that downregulation of TGF-β signaling components accompanies the development of aortic pathology in young Tgfbr2 G357W/+ mice. Methods: We performed anatomic and gene-expression studies on 8- and 12-wk-old Tgfbr2 G357W/+ mice and wild type (WT) littermates. For anatomic studies, mice were perfusion-fixed with formalin, and aortic length was measured in situ. Aortic roots as well as ascending (ASA), descending thoracic (DTA) and abdominal aortas (AA) were then embedded in OCT. Frozen sections were stained with H & E. External and internal elastic lamina lengths, aortic wall thickness and medial areas were measured. For gene expression studies, mice were saline-perfused, and the aortic root, ASA, and arch were snap frozen en bloc. RNA was extracted and TGF-β ligand and receptor mRNA were measured. Results: LDS mice (12 wk old; n = 7-9 vs 12 WT) had elongated ASA, arch, and DTA (~20%; P≤0.02), their aortic roots were dilated (20%; P<0.001), and their DTA wall thickness and medial areas were decreased (15%; P<0.01). No aortic wall hematomas were observed, and Prussian Blue staining was absent in aortic sections. mRNA encoding Tgfb1 , Tgfb2, Tgfbr1, Tgfbr3, Serpine1 , and LoxL1 were decreased in LDS mouse aortas (20-34%; P<0.05 for all; n=9-10). LDS mice (8 wk old; n = 10 vs 12 WT) had only borderline decreased aortic Tgfbr1 mRNA. Conclusions: In Tgfbr2 G357W/+ mice, development of aortic pathology is accompanied by decreased expression of several TGF-β signaling pathway components. These data suggest that the G357W loss-of-function allele causes aortopathy via an early reduction of aortic TGF-β signaling.

MRI-derived aortic characteristics after pregnancy: The AMBITYON study.

Pregnancy and pregnancy complications have been associated with increased arterial stiffness even at young age. In this study we assessed the impact of parity on CMR-derived aortic characteristics as early markers of atherosclerosis and arterial stiffness in healthy women between 25 and 35 years. We studied 68 women who participated in the AMBITYON study, a prospective population-based cohort study for assessment of atherosclerotic burden by MRI and traditional CVD risk factors in healthy, young adults. Of these women, 40 (58.8%) were nulliparous, 13 (19.1%) were primiparous and 15 (22.1%) were multiparous. Descending thoracic aortic wall thickness (AWT) and pulse wave velocity (PWV) were measured using 3.0T CMR. AWT measurements were similar between nulliparous women and primi- or multiparous women (1.6 mm ± 0.2 mm vs. 1.6 mm ± 0.2 mm; p = 0.79). Correction for age and systolic blood pressure did not change these results. Applying percentile based cut-off values showed a non-significant increase in AWT in parous women. PWV measurements did not differ between nulliparous women and parous women (4.5 m/s ± 0.7 m/s vs. 4.5 m/s ± 0.8 m/s; p = 0.78). Correction for age and systolic blood pressure did not influence these results. Using percentile based cut-off values, showed an increasing likelihood of higher PWV-values in parous women, although not statistically significant. Direct measurement of aortic AWT and PWV by CMR showed no difference between nulliparous and parous women, probably indicating limited effect of pregnancy on arterial stiffness and early markers of atherosclerosis. Netherlands Trial Register (NTR) number: 4742.

Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension.

Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4-/-) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4-/- animals. In the present study, we further characterized the hearts and aortas from these animals. Hypertrophy of cardiomyocytes, together with perivascular fibrosis and inflammation was observed in the Ang II-treated Thbs4-/- hearts. In the aortas, an increase in the aortic wall cross-sectional area (CSA) and wall thickness of the Ang II-treated Thbs4-/- mice was found. More detailed investigation of the Ang II-treated Thbs4-/- aortas also revealed the appearance of aortic dissections in the outer medial layer of the arteries, as well as pronounced inflammation. No differences were found in several other extracellular matrix-related parameters, such as number of elastin breaks or stress-strain relationships. However, at the ultrastructural level, collagen fibers showed alterations in diameter in the media and adventitia of the Ang II-treated Thbs4-/- mice, in the area prone to dissection. In conclusion, we identified TSP-4 as an important protein in the development of cardiac hypertrophy and aortic dissections in Ang II-induced hypertension.

Imaging Insights on the Aorta in Aging.

The aorta has 2 main functions, conduit and cushion, and is designed to transmit blood to the periphery and buffer pulsatile stress from ventricular contraction. In the interaction between the structural and functional changes of the aorta, aging and disease processes impact on aortic material properties and hemodynamics. For a comprehensive assessment of changes in aortic structure and function associated with aging and disease, noninvasive cardiovascular imaging techniques, especially magnetic resonance imaging, have recently been developed. Magnetic resonance imaging allows for direct and accurate measurement of different aortic characteristics including structural measures such as aortic area or volume, aortic length, curvature, and aortic wall thickness and functional measures such as aortic strain, distensibility, and pulse wave velocity. Excellent reproducibility of magnetic resonance imaging methods allows us to assess the response of the whole aorta to both pharmacological and nonpharmacological therapies. Aortic flow and functional assessment could be added to clinical routine cardiac magnetic resonance as a comprehensive imaging modality primarily performed for the noninvasive evaluation of left ventricular function, left ventricular load, and vascular/ventricular coupling. New techniques such as 4-dimensional flow could provide and further elucidate the combined age-related effects of altered aortic geometry and function. This following review will describe the pathophysiological aspects of the aorta and the ability, value, and prospects of cardiovascular imaging, especially magnetic resonance imaging, to study age-related changes in aortic structure and function and assess the relationship between these alterations and cardiovascular disease.

Effects of Excessive Choline Administration on Cardiovascular Risk Factors and Hepatic Cholesterol Metabolism in Female SD Rats

Choline has been considered to be linked to an increase of cardiovascular risk. It can be metabolized to trimethylamine by gut microbiota and further converted by hepatic flavin monooxygenase 3 (FMO3) to trimethylamine‐N‐oxide (TMAO) which is known to be a putative promoter of cardiovascular disease. However, the effects of excessive choline administration on the cardiovascular risk, especially in SD rats, have been little studied. The purpose of this study was to evaluate the effects of excessive choline administration on serum TMAO level, aortic wall thickness, and expression of hepatic genes responsible for cholesterol metabolism in female SD rats. Twenty female SD rats were fed AIN93‐G diet with or without various concentrations of choline chloride (1.5%, 2.25%, 3%) (w/w) in autoclaved water for 8 weeks. Aortic wall section of the rat was stained by hematoxylin and eosin. Serum TMAO and choline levels were determined by UPLC‐Synapt G2‐Si. Hepatic mRNA expression of FMO3, farnesoid X receptor (FXR), liver X receptor α (LXRα), sterol regulatory element‐binding protein 2 (SREBP‐2), cholesterol 7 alpha‐hydroxylase (CYP7A1), and low‐density lipoprotein receptor (LDLR) was determined by quantitative PCR. Serum TMAO level was significantly (p<0.05) higher in the rat fed 1.5% choline‐containing water (1.5C) than control group (25.03 ± 14.27 vs. 0.34 ± 0.35 μM). However, serum choline levels were not significantly (p>0.05) different (18.01 ± 7.15 vs. 23.13 ± 11.89 μM). Aortic wall of the 1.5C seemed to be thicker than the control group. Relative mRNA expression of CYP7A1 was down‐regulated in the 1.5C compared to the control group (0.32 ± 0.24 vs. 1.00 ± 0.56, p<0.05), whereas that of FXR was up‐regulated (1.59 ± 0.60 vs. 1.00 ± 0.39, p<0.05). However, mRNA expressions of hepatic FMO3, LDLR, LXRα, and SREBP‐2 were not significantly (p>0.05) different. Excessive choline administration seemed to be able to affect cardiovascular system in female SD rats via production of TMAO and regulation of CYP7A1 and FXR. Additional research about secondary bile acid produced by gut bacteria is needed.Support or Funding InformationThis research has been supported by National Research Foundation of Korea (NRF‐ 2017R1D1A1B03028407) funded by the Ministry of Education of Korea.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

EVALUATION OF PHYSICAL EXERCISE BY SWIMMING PREVIOUSLY TO MYOCARDIAL INFARCTION

Physical exercise prior to myocardial infarction (MI) protects against the IM scar, prevents cardiac remodeling and attenuates systolic dysfunction and diastolic activity in rats. Evaluate the influence of physical training by swimming, performed prior to MI, on the growth of cardiac masses, pulmonary and hepatic water content. Characterize the echocardiographic changes indicative of cardioprotection induced by physical training prior to myocardial infarction. Young rats weighing between 170 and 190 grams, from the Experimental Models Development Center (CEDEME) of the Federal University of São Paulo, were used. The animals were kept in boxes with water and rations in a temperature controlled environment. They were distributed in four experimental groups: non‐infarcted sedentary (SS); Sedentary infarcted (IMS); Trained non‐infarcted (SE); Infarcted Training (IME) The animals were submitted to a period of adaptation to the swimming exercise, later those belonging to the SE and IME groups swam for 90 minutes, this time was maintained until five weeks were completed. After this period the maximum physical capacity (MCF) was again evaluated and then the rats were submitted to myocardial infarction (MI) surgery. The method of production of IM was based on the work of Johns and Olson (1954). After three weeks of infarction the animals were submitted to Doppler echocardiography and were sacrificed for the analysis of the wet and dry weight of the heart, lungs and liver. The data were statistically evaluated, one‐way ANOVA followed by Tukey's test, and significant values of (p<0,05) were considered. After the training period prior to MI, the animals exercised SE (2,317 ± 275 seconds) and IME (3,104 ± 281 seconds) had an increase (p ≤ 0.001) in MCF compared to SS sedentary animals (378 ± 43 seconds) and IMS (341 ± 25 seconds), respectively. These results indicate that the protocol was effective in increasing the cardiorespiratory capacity of the exercised animals. The atrial masses of the infarcted animals were higher than those of the non‐infarcted animals (p ≤ 0.001). The right ventricular (RV) mass values of SE, IMS and IME animals were higher than the values for the SS group (p ≤ 0.001). There was hypertrophy (12%) of the left ventricle (LV) of the SE rats in relation to the SS (p = 0.008). The results of the IMS and IME groups related to the cardiac morphology indicated significant LV dilation and decreased LV wall thickness (p ≤ 0.001) in relation to SS and SE animals. No significant differences were observed in the comparisons of aortic diameters, left atrial and LV posterior wall thickness between groups. The water contents of the lungs and liver did not differ significantly between the four experimental groups. The results related to the systolic function indicated that there was a significant loss (p ≤ 0.001) of the shortening fraction and the shortening fraction of the transverse area indicating clear systolic dysfunction, not prevented by physical exercise. Values for diastolic function in infarcted animals were significantly worse than those recorded in non‐infarcted animals (p<0,05). The protocol of physical training per swimming, imposed prior to MI, did not prevent the cardiac remodeling of infarcted rats and does not prevent cardiac remodeling or systolic and diastolic dysfunction evaluated by Doppler echocardiography.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

CT analysis of the aorta in giant-cell arteritis: a case-control study

Giant cell arteritis (GCA) is a large-vessel vasculitis whose diagnosis is confirmed by temporal artery biopsy. However, involvement of large vessels, especially the aorta, can be shown by imaging, which plays an increasing role in GCA diagnosis. The threshold above which aortic wall thickening, as measured by computed tomography (CT), is considered pathological is controversial, with values ranging from 2 to 3 mm. This study assessed aortic morphology by CT scan and its diagnostic value in GCA. Altogether, 174 patients were included (64 with GCA, 43 with polymyalgia rheumatica and 67 controls). All patients had a CT scan at diagnosis or at inclusion for controls. Aortic wall thickness, aortic diameter and scores for atheroma were measured. Assessor was blinded to each patient's group. Aortic diameters and atheroma scores were similar between groups. Aortic wall thickness was greater in the GCA group, even after the exclusion of GCA patients with aortic wall thickness ≥3 mm. The receiver operating characteristic (ROC) curve showed that a wall thickness of 2.2 mm was the optimal threshold to diagnose GCA (sensitivity, 67%; specificity, 98%). Measuring aortic wall thickness by CT scan is effective to diagnose GCA. The optimal threshold to regard aortic wall thickening as pathological was ≥2.2 mm. • Imaging, including CT scan, plays an increasing role in GCA diagnosis • CT measurement of aortic wall thickness is useful to diagnose GCA • A 2.2-mm threshold allows the diagnosis of thickened aortic wall in GCA.

Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort.

Vascular ageing is characterized by arterial stiffening, dilation, and arterial wall thickening. We investigated the extent to which these changes are related and their heritability during 5 year follow-up in the Twins UK cohort. Carotid-femoral pulse wave velocity (PWVcf), carotid diameter, carotid distensibility, and carotid intima-media thickness (IMT) were measured in 762 female twins (mean age 57.9 ± 8.6 years) at two time-points over an average follow-up of 4.9 ± 1.5 years. Magnetic resonance imaging (MRI) was performed in a sub-sample of 38 women to measure aortic pulse wave velocity (PWVaorta), diameter, and wall thickness. Heritability of changes in arterial wall properties was estimated using structural equation modelling. Annual increases in PWVcf, carotid diameter, distensibility, and IMT were 0.139 m/s, 0.028 mm, -0.4 kPa-1, and 0.011 mm per year, respectively. In regression analysis, predictors of progression in PWVcf included age, mean arterial pressure (MAP), and heart rate (HR) at baseline, and progression in MAP, HR, and body mass index (BMI). Predictors of progression in IMT included progression in MAP, BMI, and triglyceride levels. Progression of PWV and distensibility correlated with progression in carotid diameter but not with IMT. Heritability of progression of PWVcf, diameter, and IMT was 55%, 21%, and 8%, respectively. In a sub-sample of women that underwent MRI, aortic wall thickness increased by 0.19 mm/year, but aortic wall thickening was not correlated with an increase in lumen diameter or PWVaorta. Arterial stiffening, as measured by PWVcf, and dilation are heritable but independent of arterial wall thickening. Genetic and cardiovascular risk factors contribute differently to progression of PWV and IMT.

Abstract P363: Visceral, but Not Subcutaneous Adiposity by Computed Tomography is Associated With Increased Aortic Wall Thickness in Psoriasis Patients

Introduction: Patients with psoriasis (PSO), an inflammatory skin disease, experience increased cardiovascular disease and obesity. Traditional measures of obesity, such as BMI and waist-to-hip ratio (WHR), do not fully capture the increased cardiovascular risk. Assessment of adipose tissue distribution via CT scan enables characterization of visceral adiposity (VAT) versus subcutaneous adiposity (SAT), which is clinically useful as excess VAT is known to be associated with cardiovascular events. Aortic Wall Thickness (AWT) is a validated measure of subclinical atherosclerosis. However, the relationship between adiposity distribution and AWT is unknown. Hypothesis: We hypothesized that VAT, but not SAT, BMI, or WHR, would be associated with increased AWT in PSO patients. Methods: Consecutive PSO patients (n=164) underwent quantification of VAT and SAT via CT, and AWT via MRI of the descending aorta. Interrelationships were analyzed via multivariable regression. Results: Patients were middle-aged (mean 50.4), predominantly male (56%), and were at low cardiovascular risk (median Framingham risk 3), despite high prevalence of hyperlipidemia (47%). VAT was significantly associated with AWT (β=0.18, p=0.04), SAT, BMI, or WHR did not demonstrate similar association. This association persisted beyond adjustment for SAT, Framingham score, insulin resistance, and systolic BP (β=0.30, p=0.03). Conclusions: Visceral adiposity demonstrated an association with AWT, a marker of early atherosclerosis, whereas subcutaneous adiposity, BMI, and WHR did not. These findings add to a growing body of literature that visceral fat and its assessment may provide incremental data for risk of subclinical CVD.

Three-Dimensional Full-Field Strain Measurements across a Whole Porcine Aorta Subjected to Tensile Loading Using Optical Coherence Tomography–Digital Volume Correlation

Optical Coherence Tomography (OCT) combined with Digital Volume Correlation (DVC) is a suitable technique to investigate the biomechanical behavior of biological tissues at the microscale. However, to characterize the whole thickness of large human or porcine arteries, the use of osmotic tissue clearing agents, such as propylene glycol, is unavoidable due to intrinsic tissue scattering of light. The mechanical response of biological tissues immersed in tissue clearing agents has been poorly investigated so far. Nevertheless, understanding the mechanisms of tissue clearing could be helpful for developing safe optical-clearing methods for possible in vivo applications. The goal of the present work is to combine OCT and DVC to measure displacement and strain fields in porcine aortic tissues immersed in polypropylene glycol and subjected to stress-relaxation uniaxial tension. Displacement and strain fields are measured across the whole thickness of the porcine aortic wall for the first time. Measurement uncertainties and optimal OCT-DVC parameters are determined to define useful technical recommendations for future similar analyses. It is known that the main effect of polypropylene glycol is a significant increase of collagen fibril packing density due to important loss of water (dehydratation). It results in a pronounced stiffening of the aortic tensile response when compared to the response of the same tissue immersed in PBS. This effect is reversible when the aortic tissue is removed from polypropylene glycol and immersed again in PBS. Another effect is a dramatic reduction of the Poisson’s effect during tensile loading. But the OCT-DVC measured strain fields also reveal heterogeneities of this effect among the different layers of the aorta. It appears that the reduced Poisson’s effect is concentrated in the media layer, whereas the adventitia and intima layer keep a usual Poisson’s effect of nearly incompressible tissues. It is concluded that further work should be conducted on how the smooth muscle cells highly present in the media layer are affected by polypropylene glycol immersion for a better understanding of these effects.

IMPROVEMENT IN SKIN DISEASE SEVERITY IS ASSOCIATED WITH REDUCED PROGRESSION OF AORTIC WALL THICKNESS IN PATIENTS WITH PSORIASIS

Psoriasis (PSO), an inflammatory disease associated with increased subclinical atherosclerosis (ATH), provides a useful in vivo model for investigating atherogenesis. Aortic wall thickness (AWT) is known to be associated with prospective cardiovascular events. The effect of modulating skin

Ischemia/reperfusion injury in male guinea pigs: An efficient model to investigate myocardial damage in cardiovascular complications

Myocardial ischemia/reperfusion (I/R) injury is the major problem that aggravates cardiac damage. Several established animal models fail to explain the similarity in disease mechanism and progression as seen in humans; whereas guinea pig shows high similarity in cardiovascular parameters. Hence, current study is aimed to develop an animal model using guinea pigs that may best correlate with disease mechanism of human myocardial I/R injury. Male guinea pigs were randomized into three groups: normal diet (ND), high fat diet (HFD) and sham; fed with respective diets for 90 days. Myocardial infarction (MI) was induced by ligating left anterior descending artery (LAD) for 30 min followed by 24 h and 7 days of reperfusion in ND and HFD groups. Electrocardiogram (ECG) showed the alterations in electrical conduction during myocardial I/R injury. Elevated levels of lactate dehydrogenase (LDH) and creatine kinase-MB ((CK-MB)) were higher in HFD compared to ND. Inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were up-regulated in I/R injury animals compared to sham. Fold change of these protein expression levels were higher in HFD compared to ND. Elevated lipid profile and increased aortic wall thickness in HFD animals depicts the risk of developing cardiovascular complications. ECG analysis strongly confirmed MI through changes in sinus rhythm that are reflected in infarcted tissue as verified through TTC staining. Thus the combination of HFD followed by I/R injury proved to be an efficient model to study pathophysiology of myocardial I/R injury with minimal tissue damage and surgical mortality.

Shortening tends to increase aortic foam cell count and wall thickness in male Wistar rats

BackgroundShortening is widely used as raw material for bread and other foods. Hypercholesterolemia increases aortic arch foam cell formation and abdominal aortic wall thickness. This study aimed to determine the effect of shortening on the number of aortic arch foam cells and abdominal aortic wall thickness in rats.MethodsThis study was of experimental posttest control group design. Twenty four male Wistar rats were randomized into 4 groups. The negative control group (C-) received standard feed, the positive control group (C+) standard high-fat feed, group T1 shortening and standard feed at a ratio of 1:5 and group T2 shortening and standard feed at a ratio of 1:10. The interventions were given for 6 weeks through gavage. The foam cell count in the aortic arch and the thickness of the abdominal aortic wall were measured. One-way ANOVA test was used to analyze the data. ResultsThere was no significant difference in the mean foam cell count of the aortic arch between the four groups C- (7.17 ± 4.17), C + (9.33 ± 7.01), T1 (11.83 ± 4.88) and T2 (9.33 ± 6.80) (p=0.598). The mean thickness of the abdominal aortic wall between the four groups C- (741.98 ± 60.67μm), C + (714.29 ± 90.59μm), T1 (838.90 ± 75.86 μm), and T2 (749.88 ± 99.37μm) also was not significantly different (p=0.110).Conclusion Shortening tends to increase the foam cell count of the aortic arch and the thickness of the abdominal aortic wall of rats.

The relationship of perivascular adipose tissue and atherosclerosis in the aorta and carotid arteries, determined by magnetic resonance imaging.

Background and aims:Imaging studies have relied on the ‘overall’ volumetric quantification of perivascular adipose tissue. We sought to assess the relationship of circumferential distribution between perivascular adipose tissue and adjacent wall thickness of carotid and aortic arteries using dedicated magnetic resonance imaging sequences.Methods:Vessel wall and perivascular adipose tissue were acquired using magnetic resonance imaging (1.5 T). Co-registered images were segmented separately, and measurements of both perivascular adipose tissue and vessel wall were obtained along radii of the vessel spaced at angles of 5° each.Results:In total, 29 patients were recruited. Perivascular adipose tissue thickness of the aorta was 3.34 ± 0.79 mm with specific pattern of ‘double peaks’ distribution, while carotid perivascular adipose tissue had no identifiable pattern with thickness of 0.8 ± 0.91 mm. Although statistically significant, the correlation between perivascular adipose tissue thickness and wall thickness in carotid arteries with normal (r = 0.040, p = 0.001) or with abnormal wall thickness (r = –0.039, p = 0.015) was merely nominal. Similarly, perivascular adipose tissue of the aorta had very weak correlation with normal aortic wall thickness (r = 0.010, p = 0.008) but not with the abnormal ones (r = −0.05, p = 0.29).Conclusion:Dissociation between the spatial distribution of perivascular adipose tissue and arterial wall thickening in the aorta and carotid arteries does not support that perivascular adipose tissue has a causal role in promoting atherosclerotic plaque via a paracrine route. Yet, perivascular adipose tissue functional properties were not examined in this study.