The aim was to evaluate the thoracic aorta in different cardiac phases to obtain the correct cardiac phase for measuring the maximum diameter required to predict aortic disease. Cardiac CT was performed on 97 patients for suspected coronary artery disease. The average diameter of ascending (AAD) and descending aorta (DAD) in the plane of pulmonary bifurcation, in the plane of the sinus junction (AAD [STJ] and DAD [STJ]), descending aorta in the plane of the diaphragm (DAD [Dia]), the diameter of the main pulmonary artery (MPAD), distance from the sternum to the spine (S-SD), and distance from the sternum to the ascending aorta (S-AAD) were assessed at 20 different time points in the cardiac cycle. Differences in aortic diameter in different cardiac phases and the correlation between aortic diameter and traditional risk factors were analyzed by the general linear mixed model. The diameter of the thoracic aorta reached the minimum at the phase of 95-0%, and reached the maximum at 30-35%. The maximum values of AAD, AAD (STJ), DAD, DAD (STJ), and DAD (Dia) were 32.51 ± 3.35 mm, 28.86 ± 3.01 mm, 23.46 ± 2.88 mm, 21.85 ± 2.58 mm, and 21.09 ± 2.66 mm, respectively. The maximum values of MPAD/AAD and DAD/AAD (STJ) were 0.8140 ± 0.1029, 0.7623 ± 0.0799, respectively. The diameter of the thoracic aorta varies with the cardiac phase. Analyzing the changes in aortic diameter, which can be done using cardiac CT, could provide a more accurate clinical measurement for predicting aortic disease.

Although heart transplantation is a gold standard for severe heart failure, there is a need for alternative effective therapies. A dielectric-elastomer aorta is used to augment the physiological role of the aorta in the human circulatory system. To this end, the authors developed a tubular dielectric elastomer actuator (DEA) able to assist the heart by easing the deformation of the aorta in the systole and by increasing its recoil force in the diastole. In vitro experiments using a pulsatile flow-loop, replicating human physiological flow and pressure conditions, show a reduction of 5.5% (47 mJ per cycle) of the heart energy with this device. Here, the controlled stiffness of the DEA graft, which is usually difficult to exploit for actuators, is perfectly matching the assistance principle. At the same time, the physiological aortic pressure is exploited to offer a prestretch to the DEA which otherwise would require an additional bulky pre-stretching system to reach high performances.

Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta.

Telocytes (TCs) are a novel type of interstitial cells, which have been recently described in a large variety of cavitary and noncavitary organs. TCs have small cell bodies, and remarkably thin, long, and moniliform prolongations called telopodes (Tps). Until now, TCs have been found in various loose connective tissues surrounding the arterioles, venules, and capillaries, but as a histological cellular component, whether TCs exist in large arteries remains unexplored.

The media of aortic wall is characterized by altering layers of elastin and smooth muscle cells (SMCs), along with collagen fibers in both layers, and plays a central role in functional and pathological remodeling such as hypertension and atherosclerosis. Because the arterial function is linked closely to the arterial wall internal structure, it is essential to investigate the alteration of the arterial microstructure during macroscopic deformation to understand cardiovascular pathologies. The present study adopted a tissue clearing method in three-dimensional mechanical characterization of rat thoracic aorta, and successfully observed changes in the structure of each of the three primary components of the aorta under intraluminal pressurization while maintaining tissue mechanical integrity and flexibility. Layers of elastic fibers and SMCs deformed greater on the intimal side than those on the adventitial side. Furthermore, there was a structural agreement in the alignment angle between SMC nuclei and elastic fibers on their intimal side, but not on the adventitial side. This is the first study that changes in the microstructure of three primary components of the aorta were visualized and evaluated through the aorta. The method established here would also be useful to understand tissue mechanics of other load-bearing soft tissues.

Blood flow in the vasculature can be characterised by dimensionless numbers commonly used to define the level of instabilities in the flow, for example the Reynolds number, Re. Haemodynamics play a key role in cardiovascular disease (CVD) progression. Genetic studies have identified mechanosensitive genes with causal roles in CVD. Given that CVD is highly heritable and abnormal blood flow may increase risk, we investigated the heritability of fluid metrics in the ascending aorta calculated using patient-specific data from cardiac magnetic resonance (CMR) imaging. 341 participants from 108 British Caucasian families were phenotyped by CMR and genotyped for 557,124 SNPs. Flow metrics were derived from the CMR images to provide some local information about blood flow in the ascending aorta, based on maximum values at systole at a single location, denoted max, and a 'peak mean' value averaged over the area of the cross section, denoted pm. Heritability was estimated using pedigree-based (QTDT) and SNP-based (GCTA-GREML) methods. Estimates of Reynolds number based on spatially averaged local flow during systole showed substantial heritability ([Formula: see text], [Formula: see text]), while the estimated heritability for Reynolds number calculated using the absolute local maximum velocity was not statistically significant (12-13%; [Formula: see text]). Heritability estimates of the geometric quantities alone; e.g. aortic diameter ([Formula: see text], [Formula: see text]), were also substantially heritable, as described previously. These findings indicate the potential for the discovery of genetic factors influencing haemodynamic traits in large-scale genotyped and phenotyped cohorts where local spatial averaging is used, rather than instantaneous values. Future Mendelian randomisation studies of aortic haemodynamic estimates, which are swift to derive in a clinical setting, will allow for the investigation of causality of abnormal blood flow in CVD.

Introduction: Vascular grafts significantly contribute to advances in vascular surgery, but none of the currently available prosthetic grafts have elastin fibers similar to native arteries. We hypothesized that a novel elastin patch could be produced after a rat decellularized thoracic aorta elastin fiber scaffold is implanted subcutaneously in rats; we tested this novel elastin patch in a rat aortic arterioplasty model. Methods: Sprague-Dawley rats (200 g) were used. Rat thoracic aortae were decellularized and sectioned at a thickness of 30 μm. A single elastin fiber scaffold was fabricated as a net (5 × 5 mm2), and then a three-layer scaffold was constructed to make a new patch. The hyaluronic acid-sodium alginate (HA/SA) hydrogel was fabricated by reacting sodium SA, HA, and CaCO3, and then the hydrogel was added to the patch to secure the elastin fibers. The patches were implanted subcutaneously in rats and harvested at day 14. The elastin patches were then implanted into the same rat's aorta and harvested at day 14; a decellularized rat thoracic aorta (TA) patch was used as a control. Sections of the retrieved patches were stained by immunohistochemistry and immunofluorescence. Results: The elastin fibers could be secured by the hydrogel. After 14 days, the subcutaneously implanted elastin patch was incorporated into the rat tissue, and H&E staining showed that new tissue had formed around the elastin patch with almost no hydrogel left. After implantation into the rat aorta and then retrieval on day 14, H&E staining showed that there was neointima and adventitia formation in both the TA and elastin patch groups. Both patches showed a similar histological structure after implantation, and immunofluorescence showed that there were CD34- and nestin-positive cells in the neointima. In both groups, the endothelial cells expressed the arterial identity markers Ephrin-B2 and dll-4; almost one-third of the cells in the neointima were PCNA-positive with rare cleaved caspase-3-positive cells. Conclusion: We demonstrated a novel approach to making elastin fiber scaffold hydrogel patches (elastin patches) and tested them in a rat aorta arterioplasty model. This patch showed a similar healing process as the decellularized TA patch; it also showed potential applications in large animals and may be a substitute for prosthetic grafts in vascular surgery.

Traumatic aorta injury (TAI) is the second most common traumatic cause of death preceded only by head injuries, being responsible for 5% to 30% of all mortalities in high-speed deceleration injuries. Multiple external factors might play a role such as impact speed, impact direction, occupant location, and presence or lack of restraining safety mechanism. Apart from these external factors, also human biological factors can influence its development. Based on the data of scientific literature, age clearly plays a role in suffering TAI, but the role of atherosclerosis-as a disease affecting the structure of the aorta-is unknown. Biomechanical properties of tissue samples of 104 aorta specimens removed during the autopsy from the posterior (Group 'A') and lateral wall (Group 'B') of descending aorta were analyzed. Specimens were examined by a Zwick/Roell Z5.0 biaxial tester. The Young's modulus (E (MPa)) was calculated using a linear regression procedure where the base of the elongation was the parallel length of the sample, the achieved maximal force (Fmax (N)), the elongation at the time of Fmax (Lmax (mm)), the force at the beginning of rupture (Fbreak (N)), the elongation at the time of Fbreak (Lbreak (mm)) were registered. Specimens were categorized based on macroscopic and microscopic appearance. In the posterior (A) samples the difference between Lbreak (p<0.001) and Lmax (p<0.001) was significant between the macroscopic group. Lbreak (p = 0.009) and Lmax (p = 0.003) showed similar pattern in the lateral (B) samples. Comparing the histological groups by the measured parameters (Fmax, Lmax, Fbreak, Lbreak) showed a significant difference in the means (p<0.001, p = 0.003, p<0.001 respectively). The study demonstrated that atherosclerosis decreases the resistance of the aorta. The rupture occurs at lower force (Fmax and Fbreak), and at shorter elongation (Lmax and Lbreak) in case of the presence of atherosclerosis. This effect is most substantial if calcification is present: the resistance of aorta affected by calcification is only two-thirds on average compared to aorta affected by the early phase of atherosclerosis. This phenomenon can be clearly explained by the weakening structure of the tunica intima.

No abstract available

Congenital abnormalities in girls and women with Turner syndrome (TS), alongside an underlying predisposition to obesity and hypertension, contribute to an increased risk of cardiovascular disease and ultimately reduced life expectancy. We observe that children with TS present a greater variance in aortic arch morphology than their healthy counterparts, and hypothesize that their hemodynamics is also different. In this study, computational fluid dynamic (CFD) simulations were performed for four TS girls, and three age-matched healthy girls, using patient-specific inlet boundary conditions, obtained from phase-contrast MRI data. The visualization of multidirectional blood flow revealed an increase in vortical flow in the arch, supra-aortic vessels, and descending aorta, and a correlation between the presence of aortic abnormalities and disturbed flow. Compared to the relatively homogeneous pattern of time-averaged wall shear stress (TAWSS) on the healthy aortae, a highly heterogeneous distribution with elevated TAWSS values was observed in the TS geometries. Visualization of further shear stress parameters, such as oscillatory shear index (OSI), normalized relative residence time (RRTn), and transverse WSS (transWSS), revealed dissimilar heterogeneity in the oscillatory and multidirectional nature of the aortic flow. Taking into account the young age of our TS cohort (average age 13 ± 2 years) and their obesity level (75% were obese or overweight), which is believed to accelerate the initiation and progression of endothelial dysfunction, these findings may be an indication of atherosclerotic disease manifesting earlier in life in TS patients. Age, obesity and aortic morphology may, therefore, play a key role in assessing cardiovascular risk in TS children.

Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development.

The extent of preservation of endothelial, smooth muscle and neurogenic function following cold storage was studied in rabbit thoracic aorta. Relaxation responses to acetylcholine and sodium nitroprusside were compared between fresh aortic rings and rings that had been stored in a refrigerator for 2-8 days at 4 degrees C. In fresh aortic rings, the addition of acetylcholine to precontracted vessels resulted in dose-dependent relaxation. The magnitude of relaxation was gradually decreased after 4-8 days of cold storage. Relaxation in response to sodium nitroprusside did not change. Following cold storage contractions of aortic rings in response to noradrenaline and phenylephrine were not reduced. Contractile responses induced by transmural nerve stimulation were gradually attenuated with the length of cold storage. Electron microscopy after 4 days showed partial damage of endothelial cells (slightly vacuolized mitochondria). After 8 days, endothelial cells were destroyed; only membranous material was present. The structure of smooth muscle cells was only partially changed even after 8 days. Sympathetic nerve endings on the 4th day were partially, but on the 8th day completely destroyed. These results suggest that after cold storage of rabbit aorta, the gradual reduction of endothelium-dependent relaxation is probably caused by a decrease in production of the endothelium-derived relaxing factor due to the destruction of endothelial cells.

Background Coarctation of the aorta coexists with other cardiac anomalies and has long-term complications, including recoarctation, which may require intervention after the primary coarctation repair. This study aims to clarify the prevalence of and risk factors for interventions related to the coarctation complex as well as late mortality in a large contemporary patient population. Methods and Results The Swedish National Register of Congenital Heart Disease was used, which comprised 683 adults with repaired coarctation of the aorta. Analysis was performed on freedom from intervention thereafter at the coarctation site, aortic valve, left ventricular outflow tract, or ascending aorta. One hundred ninety-six (29%) patients had at least 1 of these interventions. Estimated freedom from either of these interventions was 60% after 50 years. The risk of undergoing such an intervention was higher among men (hazard ratio, 1.6 [95% CI, 1.2-2.2]). Estimated freedom from another intervention at the coarctation site was 75% after 50 years. In women, there was an increase in interventions at the coarctation site after 45 years. Patients who underwent one of the previously mentioned interventions after the primary coarctation repair had poorer left ventricular function. Eighteen patients (3%) died during follow-up in the register. The standardized mortality ratio was 2.9 (95% CI, 1.7-4.3). Conclusions Interventions are common after coarctation repair. The risk for and time of interventions are affected by sex. Our results have implications for planning follow-up and giving appropriate medical advice to the growing population of adults with repaired coarctation of the aorta.

This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10(-10) M-10(-5) M) showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression.

Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl₂ caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGFβ signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress.

Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV.

Stretch-elicited intracellular calcium ([Ca(2+)](i)) changes in individual smooth muscle cells in a ring of aorta were measured simultaneously with the force developed by the ring. A phasic increase in [Ca(2+)](i) was observed in 30% of the cells and a sustained one in 10%. Depletion of intracellular calcium store by thapsigargin and caffeine decreased phasic and increased sustained calcium responses. The inhibition of calcium entry either by stretching the aorta in a calcium-free medium or by the inhibition of stretch-activated, non-selective cationic channels by 5 microM GsMtx-4 toxin, decreased the proportion of sustained [Ca(2+)](i) responses but increased transient responses. In this condition, a third of the cells responded to stretch by a bursts of [Ca(2+)](i) spikes. The decrease of calcium influx triggered the generation of burst of calcium spikes after the application of stretch steps to the vascular wall. We conclude that progressive recruitment of smooth muscle cells is the mechanism underlying the force-generating part of the myogenic response. Two types of stretch-elicited calcium responses were observed during the recruitment of the smooth muscle cells. One was a phasic calcium discharge generated by the sarcoplasmic reticulum. The second was a tonic response produced by the activation of the stretch-sensitive cationic channels allowing extracellular Ca(2+) entry.

Functional and quantitative alterations and senescence of circulating and expanded endothelial progenitor cells (EPC), as well as systemic and tissue modifications of angiogenetic and inflammatory molecules, were evaluated for predicting age-related vessel wall remodeling, correlating them to intima media thickness (IMT) in the common carotid artery (CCA), a biomarker of early cardiovascular disease and aortic root dilation.

Thoracic aortic disease is an important cause of morbidity and mortality in the US, and aortic diameter is a heritable contributor to risk. Could a polygenic prediction of ascending aortic diameter improve detection of aortic aneurysm?

Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (hazard ratio = 1.43 per s.d., confidence interval 1.32-1.54, P = 3.3 × 10-20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.