Thoracic Aortic Stiffness Research Articles

OxLDL/LOX-1 Mediated Sex, Age, and Cell Dependent Alterations in Mouse Thoracic Aortic Vascular Reactivity, Stiffness, and Remodeling

Elevated oxidized low-density lipoprotein (oxLDL) is a risk factor and component that worsens cardiovascular disease states. OxLDL can elicit its detrimental action, via lectin-like oxLDL receptor 1 (LOX-1) and has been shown to disrupt vascular function. In this study, we determined whether oxLDL, via LOX-1, alters aortic vascular reactivity and determined if sex differences exist. Thoracic aortic endothelium-intact or -denuded ring segments were isolated from intact C57BL/6J female and male mice and incubated with oxLDL ex vivo (50ug/dL; 2h). Using wire myography, cumulative concentration-response curves to phenylephrine (PE) were generated to determine contractile responses. From these curves, the EC50 was determined and used to contract rings to assess acetylcholine (ACh) dependent relaxation. Calculated aortic stiffness and remodeling, as well as mRNA expression of vasoactive and pro-inflammatory mediators were assessed. BI-0115 (10μM; selective LOX-1 inhibitor) was used to determine LOX-1 dependence. In this study, we investigated the effects of oxidized low-density lipoprotein (oxLDL) via the LOX-1 receptor on murine thoracic aortic vasoreactivity, stiffness, and remodeling across age and sex. Our results demonstrate a differential sex, age, endothelial cell, and LOX-1 dependent alterations to the effcacy of PE-induced contractile responses and ACh-mediated vasorelaxation in the thoracic aortic rings following oxLDL exposure. Additionally, we observed a distinct sex and age effect on thoracic aortic stiffness following exposure to oxLDL. There was also a sex effect on calculated vessel diameter, as well as an age effect on oxLDL-mediated inward remodeling that was LOX-1 dependent. We also observed an oxLDL and age dependent increase in LOX-1, IL-6, endothelin-1 (ET-1), and ET-1 receptor alpha and beta mRNA expression. Thus, LOX-1 inhibition and the resulting attenuation of oxLDL/endothelial-mediated alterations in aortic function suggests that there are differential sex differences in the role of oxLDL/LOX-1 in the thoracic aorta of male and female mice. In conclusion, acute exposure to oxLDL led to altered vasoreactivity, endothelial dysfunction, and changes in aortic stiffness and remodeling. These effects were in-part age, sex, endothelial, and LOX-1 dependent. This study reveals potential complex interactions in oxLDL/LOX-1-mediated vascular responses that could serve as potential therapeutic intervention for vascular diseases such as atherosclerosis. University of Arizona Valley Research Partnership Grant VRP37 P2 (RJG), American Heart Association 19AIREA34480018 (RJG), UA VRP Grant VRP55 P1a (TSW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Chronic Obstructive Pulmonary Disease in Heart Failure With Preserved Ejection Fraction

COPD often coexists with HFpEF, but its impact on cardiovascular structure and function in HFpEF is incompletely understood. We aimed to compare cardiovascular phenotypes in patients with Chronic Obstructive Pulmonary Disease (COPD), Heart Failure with Preserved Ejection Fraction (HFpEF), or both. We studied 159 subjects with COPD alone (n = 48), HFpEF alone (n = 79) and HFpEF + COPD (n = 32). We used MRI and arterial tonometry to assess cardiac structure and function, thoracic aortic stiffness, and measures of body composition. Relative to participants with COPD only, those with HFpEF with or without COPD exhibited a greater prevalence of female sex and obesity, whereas those with HFpEF + COPD were more often African-American. Compared to the other groups, participants with HFpEF and COPD demonstrated a more concentric LV geometry (LV wall-cavity ratio 1.2, 95%CI: 1.1-1.3; p = 0.003), a greater LV mass (67.4, 95%CI: 60.7-74.2; p = 0.03, and LV extracellular volume (49.4, 95%CI: 40.9-57.9; p = 0.002). Patients with comorbid HFpEF + COPD also exhibited greater thoracic aortic stiffness assessed by pulse-wave velocity (11.3, 95% CI: 8.7-14.0 m/s; p = 0.004) and pulsatile load imposed by the ascending aorta as measured by aortic characteristic impedance (139 dsc; 95%CI=111-166; p = 0.005). Participants with HFpEF, with or without COPD, exhibited greater abdominal and pericardial fat, without difference in thoracic skeletal muscle size. In conclusion, individuals with co-morbid HFpEF and COPD have a greater degree of systemic large artery stiffening, LV remodeling, and LV fibrosis than those with either condition alone.

Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Aortic Aneurysm Susceptibility.

Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness.Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed.Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening.Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.

Aortic stiffness in adolescent Turner and Marfan syndrome patients.

Turner syndrome (TS) and Marfan syndrome (MFS) are partially characterized by aortopathies with a risk of developing severe aortic dilation, stiffness and consequent dissection and aneurysm formation. The incidence of a bicuspid aortic valve (BAV) is also increased in TS. We investigated aortic stiffness in teenage TS and MFS patients and evaluated to what degree stiffness in TS patients is augmented by the presence of a BAV. Fifty-seven patients with TS (n = 37) and MFS (n = 20), as well as 22 controls with similar age and size distribution underwent evaluation of thoracic aortic stiffness using phase-contrast magnetic resonance imaging. Calculated stiffness indices including pulse wave velocity (PWV), distensibility and relative area change (RAC) were collected to characterize the ascending aorta and descending aorta. PWV was also determined to evaluate global aortic arch stiffness. Patients with TS had reduced distensibility (0.43 vs 0.58%/mmHg, P < 0.05) and RAC (21 vs 29%, P < 0.01) in the ascending aorta when compared with normal controls. Similarly, patients with MFS had reduced ascending aortic distensibility (0.39 vs 0.58%/mmHg, P < 0.05) and RAC (22 vs 29%, P < 0.05). There were no differences in measured PWV in the ascending aorta. Patients with TS had significantly elevated PWV measured in the aortic arch when compared with controls (2.7 vs 1.9 m/s, P < 0.05). Patients with MFS had more prominent elevation in aortic arch PWV (4.2 vs 1.9 m/s, P < 0.01). The descending aortas had decreased distensibility (0.36 vs 0.55%/mmHg, P < 0.05) and RAC (18 vs 25%, P < 0.01) only in MFS patients. Additionally, 18 TS patients with a BAV were compared with 19 TS patients with a trileaflet aortic valve, without significant differences observed in any of the considered stiffness indices. TS and MFS teenage patients display evidence of increased aortic stiffness. In TS patients, this is focused in the ascending aorta and is independent of the presence of a BAV. MFS patients display a generalized reduction in compliance of the entire aorta.

Impact of different coarctation therapies on aortic stiffness: phase-contrast MRI study.

Coarctation of the aorta has been associated with increased thoracic aortic stiffness in adolescents and young adults. However, the effects of different therapeutic strategies on aortic stiffness in a young population is unknown. This study aimed to non-invasively assess aortic stiffness between different repair or intervention strategies in patients with coarctation of the aorta. Forty-nine coarctation patients who underwent either surgery (n = 26), balloon angioplasty (n = 14), or stent implantation (n = 12), and 26 age- and size-matched normotensive healthy controls underwent evaluation of thoracic aortic stiffness and flow hemodynamics via phase-contrast cardiac magnetic resonance. In children who had undergone surgical repair or balloon angioplasty, ascending aortic stiffness was increased when measured via pulse wave velocity (PWV) when compared to normal controls (all P < 0.05). Furthermore, ascending aortic distensibility and relative area change (RAC) was significantly lower in surgically and balloon treated groups (both P < 0.01). Stiffness (PWV), distensibility, and RAC in the ascending aorta were not statistically different between stented patients and controls. The ascending aorta of children following surgical repair or balloon angioplasty demonstrated signs of elevated stiffness, whereas those treated by stent implantation showed no difference in stiffness markers when compared to normal controls.

Comparative Analysis of Porcine and Human Thoracic Aortic Stiffness

To compare porcine and human thoracic aortic stiffness using the available literature. The available literature was searched for studies reporting data on porcine or human thoracic aortic mechanical behaviour. A four fibre constitutive model was used to transform the data from included studies. Thus, equi-biaxial stress stretch curves were generated to calculate circumferential and longitudinal aortic stiffness. Analysis was performed separately for the ascending and descending thoracic aorta. Data on human aortic stiffness were divided by age <60 or ≥60 years. Porcine and human aortic stiffness were compared. Eleven studies were included, six reported on young porcine aortas, four on human aortas of various ages, and one reported on both. In the ascending aorta, circumferential and longitudinal stiffness were 0.42±0.08MPa and 0.37±0.06MPa for porcine aortas (4-9 months) versus 0.55±0.15MPa and 0.45±0.08MPa for humans <60 years, and 1.02±0.59MPa and 1.03±0.54MPa for humans ≥60 years. In the descending aorta, circumferential and longitudinal stiffness were 0.46±0.03MPa and 0.44±0.01MPa for porcine aortas (4-10 months) versus 1.04±0.70MPa and 1.24±0.76MPa for humans <60 years, and 3.15±3.31MPa and 1.17±0.31MPa for humans ≥60 years. The stiffness of young porcine aortic tissue shows good correspondence with human tissue aged <60 years, especially in the ascending aorta. Young porcine aortic tissue is less stiff than human aortic tissue aged ≥60 years.

Extracellular Matrix Disarray as a Mechanism for Greater Abdominal Versus Thoracic Aortic Stiffness With Aging in Primates

Increased vascular stiffness is central to the pathophysiology of aging, hypertension, diabetes mellitus, and atherosclerosis. However, relatively few studies have examined vascular stiffness in both the thoracic and the abdominal aorta with aging, despite major differences in anatomy, embryological origin, and relation to aortic aneurysm. The 2 other unique features of this study were (1) to study young (9±1 years) and old (26±1 years) male monkeys and (2) to study direct and continuous measurements of aortic pressure and thoracic and abdominal aortic diameters in conscious monkeys. As expected, aortic stiffness, β, was increased P<0.05, 2- to 3-fold, in old versus young thoracic aorta and augmented further with superimposition of acute hypertension with phenylephrine. Surprisingly, stiffness was not greater in old thoracic aorta than in young abdominal aorta. These results can be explained, in part, by the collagen/elastin ratio, but more importantly, by disarray of collagen and elastin, which correlated best with vascular stiffness. However, vascular smooth muscle cell stiffness was not different in thoracic versus abdominal aorta in either young or old monkeys. Thus, aortic stiffness increases with aging as expected, but the most severe increases in aortic stiffness observed in the abdominal aorta is novel, where values in young monkeys equaled, or even exceeded, values of thoracic aortic stiffness in old monkeys. These results can be explained by alterations in collagen/elastin ratio, but even more importantly by collagen and elastin disarray.

Abstract 246: Thoracic versus Abdominal Aortic Stiffness in Young and Old Non-Human Primates

We demonstrated that thoracic aortic stiffness is increased in aging monkeys, with the mechanism involving increased vascular smooth muscle cell (VSMC) stiffness. In view of the importance of increased abdominal aortic stiffness to greater incidence of abdominal aortic aneurysms, the goal of this investigation was to determine differences in thoracic vs. abdominal aortic stiffness in young and old monkeys (fascicularis and rhesus). Most prior studies on aortic stiffness have been conducted in vitro or in anesthetized animals with indirect measurements of stiffness. A novel feature of the current investigation was to measure aortic diameter and pressure instantaneously and continuously in chronically instrumented, conscious young (n=25, 5-12yrs) and old male (n=21, &gt;24yrs) monkeys, instrumented with aortic pressure gauges and ultrasonic aortic diameter crystals on the thoracic and abdominal aorta. The aortic stiffness index, β[[Unable to Display Character: &amp;#61484;]][[Unable to Display Character: &amp;#61472;]]calculated as a ratio of systolic and diastolic aortic pressures and diameters, was markedly greater, p&lt;0.05, in abdominal, compared with thoracic, aorta in both young (33±5.0 in abdominal vs. 14±2.2 in thoracic) and old monkeys (57±6.3 in abdominal vs. 34±0.4 in thoracic). Although both thoracic and abdominal aortic stiffness were greater in old monkeys, p&lt;0.05, surprisingly, abdominal aortic stiffness in young monkeys (33±5.0) was equal to thoracic aortic stiffness in old monkeys (34±0.4). Using atomic force microscopy, aortic VSMC stiffness was 2 fold greater, p&lt;0.05, in old monkeys vs. young monkeys, but there were no differences in abdominal vs. thoracic aortic VSMC stiffness in either young or old monkeys. In summary, as expected, aging increased aortic stiffness, with the mechanism, in part, due to increased VSMC stiffness. However, aortic stiffness was increased more in the abdominal than thoracic aorta both in young and old monkeys, with the magnitude of the increase in the abdominal aorta of the young monkeys, similar to that which occurs with aging in the thoracic aorta. These findings point out the major differences in stiffness along the aorta and have relevance to the greater frequency of abdominal aortic aneurysms.

Abstract 18304: Assessment of Age-Related Aortic Stiffness With Magnetic Resonance Imaging

Background: Several methods have emerged to assess aortic stiffness with magnetic resonance imaging (MRI). We aimed to compare 3 MRI methods to assess thoracic aortic stiffness as an index of arterial aging.[[Unable to Display Character: ]] Methods: We studied 97 patients referred for a clinically-indicated cardiac MRI at 1.5 T. We assessed aortic stiffness via the following Methods: (1) Pulse wave velocity (PWV) measurements from the foot-to-foot transit-time (PWV-TT) of flow between the ascending and distal thoracic descending aorta, measured via in-plane MRI phase-contrast imaging; (2) PWV estimations via the flow-area method (PWV-QA), where local PWV is computed as the ratio between ascending aortic pulsate flow (assessed with through-plane phase-contrast imaging) and change in cross-sectional area (assessed with steady-state free precession cine imaging) during the reflection-free period of the cardiac cycle (early systole); (3) Ascending aortic distensibility, measured as the fractional aortic lumen area change (assessed with steady-state free precession imaging) divided by central pulse pressure (measured with carotid applanation tonometry).[[Unable to Display Character: ]] Results: Semi-automated segmentation of aortic steady-state free precession cine images using active contour methods was feasible in 72.2% of cases, whereas transit-time estimations were feasible in all cases studied. Among cases with complete data,[[Unable to Display Character: ]]coefficients of correlation (R) with age were as follows: 0.49 for PWV-TT, 0.43 for PWV-QA and 0.62 for aortic distensibility (all P&lt;0.0001). However, after adjustment for distending pressure (mean arterial pressure), partial coefficients of correlation (R) with age were as follows: 0.39 for PWV-TT (P=0.001), 0.61 for PWV-QA (P&lt;0.0001) and 0.56 for aortic distensibility (P&lt;0.0001). Conclusion: Local ascending aortic distensibility or PWV assessments using the area-flow method appear to be more robust indicators of age-related large artery stiffening than the transit-time method based on in-plane phase-contrast aortic imaging. However, semi-automated aortic segmentation is not feasible in a significant proportion of cases, underscoring the need to develop more robust MRI methods to quantify aortic distension.

914Assessment of aortic stiffness by cardiovascular magnetic resonance in coronary artery disease and its value in prediction of myocardial infarction size

Aim: to evaluate different parameters of thoracic aortic stiffness derived from cardiovascular magnetic resonance (CMR) imaging in patients with myocardial infarction (MI) and evaluate their values in prediction of MI size. Methods: 60 subjects were prospectively included, and classified into 2 groups: subjects without CAD (N-CAD, n = 27), subjects with MI (MI, n = 33). The regional pulse wave velocity (rPWV) in the aortic arch was measured using velocity encoded cardiovascular magnetic resonance. ART-FUN software was used for automated spatial segmentation of aorta, combining the estimation of the transit time and the length of the aortic arch. The temporal evolution of the aortic area during one cardiac cycle provides the estimation of other local rigidity indices: distensibility of the ascending aorta (D-AA) and distensibility of descending aorta (D-DA), strain of ascending (S-AA) and descending aorta (S-DA), local PWV in ascending (PWV-AA). The size of myocardial infarction (surface) was evaluated by left ventricular late enhancement of gadolinium (LELV) using phase sensitive inversion recovery MRI sequences. Results: Age of the population was 56.7 ± 14.5 years. The proportion of males and smoker in MI was higher than N-CMD group (p = 0.001, p = 0.013 respectively). There was no significant difference of all aortic stiffness parameters between the two groups (p = NS). In MI group, PWV-AA was inversely correlated with S-AA and D-AA (r = 0.6, p = 0.001; r = 0.8,p = 0.0001). The rPWV is correlated with age (r = 0.5, p = 0.0001). S-AA and D-AA were inversely correlated with smoking (r = -0.6, p = 0.001; r = -0.4, p = 0.02). Multivariate analysis showed that age, aortic stiffness (increased rPWV and decreased D-AD) were independent risk factors of higher MI size (p = 0.01, p = 0.02, p = 0.03 respectively). Conclusion: CMR imaging is a non-invasive technique useful for the evaluation of local and regional aortic stiffness. Aortic stiffness and age are independent predictors of the myocardial infraction size.

Anti-stiffness effect of apocynin in deoxycorticosterone acetate-salt hypertensive rats via inhibition of oxidative stress

This study sought to determine if apocynin, a nicotinamide adenine dinucleotide phosphate oxidase inhibitor, would attenuate arterial stiffness in salt-sensitive hypertensive rats via structural and functional changes in conduit arteries. We showed that tail blood pressure was significantly higher in deoxycorticosterone acetate-salt-induced hypertensive (DSH) rats compared with the sham control group (P<0.01). Morphological analysis and biochemical assay showed that large arteries in DSH rats underwent significant remodeling including increased medial thickness in carotid arteries compared with the control rats (194.25±5.66 vs. 120.48±7.93 μm, P<0.05) and increased collagen deposition in thoracic aorta (1.03±0.09 vs. 0.85±0.04 mg cm(-1), P<0.05). These changes were associated with increases in reactive oxygen species (ROS) level and increased thoracic aortic stiffness compared with the control rats (6.21±0.79 m s(-1) vs. 4.64±0.59 m s(-1), P<0.01). Treatment with apocynin significantly prevented ROS increases and collagen deposition (0.84±0.04 vs. 1.03±0.09 mg cm(-1), P<0.05), and reduced arterial stiffness as shown by decreased pulse wave velocity in the thoracic aorta (5.31±0.88 vs. 6.21±0.79 m s(-1), P<0.01). Additionally, apocynin prevented carotid artery wall thickening (58.57±3.40 vs. 78.89±4.10 μm, P<0.05). In conclusion we have shown that increased ROS level is associated with increased aortic stiffness, and deposition of collagen in the aortic arterial wall in DSH rats. Apocynin prevented ROS increases and arterial stiffness in DSH rats. Antioxidant therapy may be a potential treatment of large arterial stiffness in salt-sensitive hypertension.

Aortic Stiffness Increases Upon Receipt of Anthracycline Chemotherapy

PURPOSE Cancer survivors exposed to anthracyclines experience an increased risk of cardiovascular (CV) events. We hypothesized that anthracycline use may increase aortic stiffness, a known predictor of CV events. PATIENTS AND METHODS We performed a prospective, case-control study involving 53 patients: 40 individuals who received an anthracycline for the treatment of breast cancer, lymphoma, or leukemia (cases), and 13 age- and sex-matched controls. Each participant underwent phase-contrast cardiovascular magnetic resonance measures of pulse wave velocity (PWV) and aortic distensibility (AoD) in the thoracic aorta at baseline, and 4 months after initiation of chemotherapy. Four one-way analyses of covariance models were fit in which factors known to influence thoracic aortic stiffness were included as covariates in the models. Results At the 4-month follow-up visit, aortic stiffness remained similar to baseline in the control participants. However, in the participants receiving anthracyclines, aortic stiffness increased markedly (relative to baseline), as evidenced by a decrease in AoD (P < .0001) and an increase in PWV (P < .0001). These changes in aortic stiffness persisted after accounting for age, sex, cardiac output, administered cardioactive medications, and underlying clinical conditions known to influence aortic stiffness, such as hypertension or diabetes (P < .0001). CONCLUSION A significant increase in aortic stiffness occurs within 4 months of exposure to an anthracycline which was not seen in an untreated control group. These results indicate that previously regarded cardiotoxic cancer therapy adversely increases thoracic aortic stiffness, a known independent predictor of adverse cardiovascular events.

Location of Arterial Stiffening Differs in Those With Impaired Fasting Glucose Versus Diabetes

OBJECTIVETo determine whether middle-aged and older individuals with impaired fasting glucose (IFG), but no clinical evidence of cardiovascular disease, exhibit abnormal changes in proximal thoracic aortic stiffness or left ventricular (LV) mass when compared with healthy counterparts.RESEARCH DESIGN AND METHODSFrom the Multi-Ethnic Study of Atherosclerosis, 2,240 subjects with normal fasting glucose (NFG), 845 with IFG, and 414 with diabetes, all aged 45 to 85 years and without preexisting coronary artery disease, underwent MRI determinations of total arterial and proximal thoracic aortic stiffness and LV mass. The presence or absence of other factors known to influence arterial stiffness was assessed.RESULTSAfter adjustment for clinical factors known to modify arterial stiffness, proximal thoracic aortic stiffness was not increased in those with IFG compared with those with NFG (1.90 ± 0.05 versus 1.91 ± 0.04 10−3 mmHg−1, respectively, P = 0.83). After accounting for clinical factors known to influence LV mass, LV mass was increased in those with diabetes relative to those with NFG (150.6 ± 1.4 versus 145.8 ± 0.81 g, P < 0.0009) but not in those with IFG in comparison with NFG (145.2 ± 1.03 versus 145.8 ± 0.81 g, P = 0.56).CONCLUSIONSMiddle-aged and older individuals with the pre-diabetes state of IFG do not exhibit abnormal proximal thoracic distensibility or LV hypertrophy relative to individuals with NFG. For this reason, an opportunity may exist in those with IFG to prevent LV hypertrophy and abnormal aortic stiffness that is observed in middle-aged and older individuals with diabetes.

214 Relation between systemic hypertension and thoracic aortic stiffness (transesophageal echocardiography — TEE)

214 Relation between systemic hypertension and thoracic aortic stiffness (transesophageal echocardiography — TEE)

214 Relation between systemic hypertension and thoracic aortic stiffness (transesophageal echocardiography — TEE)

214 Relation between systemic hypertension and thoracic aortic stiffness (transesophageal echocardiography — TEE)