BCL11B Regulates Arterial Stiffness and Related Target Organ Damage.
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ABSTRACT:
SUBMITTER: Valisno JAC
PROVIDER: S-EPMC7969164 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
BCL11B Regulates Arterial Stiffness and Related Target Organ Damage.
Valisno Jeff Arni C JAC May Joel J Singh Kuldeep K Helm Eric Y EY Venegas Lisia L Budbazar Enkhjargal E Goodman Jena B JB Nicholson Christopher J CJ Avram Dorina D Cohen Richard A RA Mitchell Gary F GF Morgan Kathleen G KG Seta Francesca F
Circulation research 20210203 6
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Project description:IntroductionLittle is known about the relationship between arterial stiffness and cardiovascular target organ damage (TOD) in the general population. The aim was to analyse the relationship between different measurements of arterial stiffness and TOD, in a general Spanish population without a history of cardiovascular event.Materials and methodsTransversal descriptive study. Through stratified random sampling, a total of 501 individuals were included. Carotid-femoral pulse wave velocity (cf-PWV) was measured using a SphygmoCor System®, the cardio-ankle vascular index (CAVI) was determined with aVasera VS-1500® and brachial-ankle pulse wave velocity (ba-PWV)was calculated through a validated equation.ResultsThe average age was 55.84 ± 14.26.The percentage of vascular TOD, left ventricular hypertrophy (LVH) and renal TOD was higher in men (p < .001). A positive correlation was obtained between carotid intima-media thickness (c-IMT) and the measurements of vascular function. In the model 1 of the logistic regression analysis, cf-PWV was associated with vascular TOD (OR = 1.15, p = .040), ba-PWV was associated with vascular TOD (OR = 1.20, p = .010) and LVH (OR = 1.12, p = .047).ConclusionsThe different measurements of arterial stiffness are highly associated with each other. Moreover, cf-PWV and ba-PWV were associated with vascular TOD, and ba-PWV with LVH, although they disappear when adjusting for cardiovascular risk factors. Key Messages There is a strong correlation between the different measurements of vascular structure and function. Carotid-femoral and brachial-ankle pulse wave velocity were positively associated with vascular target organ damage, the latter was also positively associated with left ventricular hypertrophy. This associations disappear when adjusting for cardiovascular risk factors.
| S-EPMC7877984 | biostudies-literature
Project description:This study aimed to explore whether brachial-ankle pulse wave velocity (baPWV) and brachial artery flow-mediated dilation (FMD) or the interaction of both parameters are associated with subclinical target organ damage (STOD) indices in patients with essential hypertension. A total of 4618 patients registered from January 2015 to October 2020 were included. baPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Whereas left ventricular hypertrophy (LVH), urine albumin-creatinine ratio (UACR), and carotid intima-media thickness (CIMT) were obtained as STOD indicators. On multivariable logistic regression analysis with potential confounders, higher quartiles of baPWV and FMD were significantly associated with an increased risk of STOD. In patients <65 years of age, the odds ratio (OR) of LVH, UACR, and CIMT ≥.9 mm for the fourth versus the first quartile of baPWV were 1.765 (1.390-2.240), 2.832 (2.014-3.813), and 3.075 (2.315-4.084), respectively. In interaction analysis, an increase in baPWV shows a progressively higher risk of STOD across the quartiles of FMD. Also, the estimated absolute risks of LVH, UACR, and CIMT ≥.9 mm for the first to fourth quartile of baPWV increased from 1.88 to 2.75, 2.35 to 4.44, and 3.10 to 6.10, respectively, in patients grouped by FMD quartiles. The addition of baPWV to FMD slightly improved risk prediction for STOD. BaPWV and FMD were independently associated with an increased risk of STOD in patients with essential hypertension especially among patients <65 years of age. Patients with elevated baPWV and decreased FMD parameters are at increased risk of STOD.
| S-EPMC8989756 | biostudies-literature
Project description:AimsPrevious cross-sectional observation identified arterial aging, indexed as pulse-wave velocity (PWV), as a key determinant of the simultaneous multiple organ damage (heart, carotid artery, and kidney). The aim of the present cohort study is to investigate trajectories of repeated measures of PWV and traditional CV risk factors in subjects who eventually presented clinical evidence of multiple organ damage in the SardiNIA study.Methods and resultsOrgan damage was measured in the heart (left ventricular hypertrophy, LVH), the common carotid artery (intima-media thickness > 0.9 mm and/or plaque), and the kidney (eGFR < 60 ml/min/1.73 m2) of 2130 men and women of a broad age range participating the SardiNIA study. SHATS was defined as the simultaneous occurrence of all the three-organ damages. Trajectory in traditional CV risk factors and PWV was analyzed retrospectively (four observations over 9 years) according to the number of organ damage (from 0 to 3). Compared to subjects with no organ damage, after controlling for traditional CV risk factors, each 1 m/s increase in baseline PWV was accompanied by a 93% higher odds of developing SHATS; and each 1 cm/s (0.01 m/s) annual increase in PWV by a 31% greater odds of developing SHATS.ConclusionsArterial stiffness, a proxy of arterial aging that can be measured clinically as PWV, is an integrated predictive marker of multiple age-associated organ damage recognized as clinical diseases.
| S-EPMC8476312 | biostudies-literature
Project description:BackgroundHypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)-related increased arterial stiffness is present in youth with elevated BP and is associated with TOD.MethodsParticipants were stratified by systolic BP into low- (systolic BP <75th percentile, n=155), mid- (systolic BP ≥80th and <90th percentile, n=88), and high-risk BP categories (≥90th percentile, n=139), based on age-, sex- and height-specific pediatric BP cut points. Clinic BP, 24-hour ambulatory BP monitoring, anthropometrics, and laboratory data were obtained. Arterial stiffness measures included carotid-femoral pulse wave velocity and aortic stiffness. Left ventricular mass index, left ventricular systolic and diastolic function, and urine albumin/creatinine were collected. ANOVA with Bonferroni correction was used to evaluate differences in cardiovascular risk factors, pulse wave velocity, and cardiac function across groups. General linear models were used to examine factors associated with arterial stiffness and to determine whether arterial stiffness is associated with TOD after accounting for BP.ResultsPulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP.ConclusionsHigher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.
| S-EPMC9378473 | biostudies-literature
Project description:BackgroundAmbulatory blood pressure monitoring (ABPM) shows a better correlation to target organ damage and cardiovascular morbidity-mortality than office blood pressure. A loss of arterial elasticity and an increase in carotid artery intima-media thickness (IMT) has been associated with increased cardiovascular morbidity-mortality. Tools have been developed that allow estimation of the retinal arteriovenous index but not all studies coincide and there are contradictory results in relation to the evolution of the arteriosclerotic lesions and the caliber of the retinal vessels. The purpose of this study is to analyze the relationship between peripheral and central arterial pressure (clinic and ambulatory) and vascular structure and function as evaluated by the carotid artery intima-media thickness, retina arteriovenous index, pulse wave velocity (PWV) and ankle-brachial index in patients with and without type 2 diabetes. In turn, software is developed and validated for measuring retinal vessel thickness and automatically estimating the arteriovenous index.Methods/designA cross-sectional study involving a control group will be made, with a posterior 4-year follow-up period in primary care. The study patients will be type 2 diabetics, with a control group of non-diabetic individuals. Consecutive sampling will be used to include 300 patients between 34-75 years of age and no previous cardiovascular disease, one-half being assigned to each group.Main measurementsage, gender, height, weight and abdominal circumference. Lipids, creatinine, microalbuminuria, blood glucose, HbA1c, blood insulin, high sensitivity C-reactive protein and endothelial dysfunction markers. Clinic and ambulatory blood pressure monitoring. Carotid ultrasound to evaluate IMT, and retinography to evaluate the arteriovenous index. ECG to assess left ventricle hypertrophy, ankle-brachial index, and pulse wave analysis (PWA) and pulse wave velocity (PWV) with the Sphigmocor System.DiscussionWe hope to obtain information on the correlation of different ABPM-derived parameters and PWA to organ target damage--particularly vascular structure and function evaluated from the IMT and PWV--and endothelial dysfunction in patients with and without type 2 diabetes. We also hope to demonstrate the usefulness of the instrument developed for the automated evaluation of retinal vascularization in the early detection of alterations in vascular structure and function and in the prognosis of middle-term cardiovascular morbidity.Trial registrationClinical Trials.gov Identifier: NCT01325064.
| S-EPMC3096907 | biostudies-literature
Project description:Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.
| S-EPMC5841863 | biostudies-literature
Project description: Not available
| S-EPMC3155491 | biostudies-literature
Project description:BackgroundVascular damage is recognized as a diagnostic landmark in systemic sclerosis (SSc), both in its limited and diffuse subtypes. Early detection at a subclinical stage with transthoracic echocardiography (TTE) and carotid femoral pulse wave velocity (cfPWV) may be helpful in therapeutic planning and management. Aim of the Study. The aim of the study was to evaluate presence of subclinical cardiovascular damage in patients with limited and diffuse SSc in comparison with a cohort of healthy individuals.MethodsConsecutive patients with limited and diffuse SSc underwent complete TTE and cfPWV and a complete review of clinical data. As controls, 23 healthy subjects with similar hemodynamic profiles were selected.Results41 patients (35 female, aged 56.9 years), 21 with diffuse and 20 with limited SSc, were recruited. Past medical history, cardiovascular risk factors, gender distribution, and disease duration were similar in the two groups as well as TTE parameters and hemodynamic indexes-cfPWV (6.5 [6-6.8] vs. 7.0 [6.2-8.5], p=0.24) and augmentation index (145.6 ± 14.2 vs. 149 ± 20.6, p=0.52). Patients with limited SSc were 10 years older than patients with diffuse SSc. In the multiple regression analysis, only age (p=0.0154) and disease duration (p=0.0467) resulted as the significant determinant of cfPWV. When compared to healthy controls, no significant difference emerged in TTE or hemodynamic indexes.ConclusionIn SSc, cfPWV increases with age, with no additional impact of pathology or subtype. Vascular damage in the SSc population is not accurately reflected in increased arterial stiffness, as evaluated with cfPWV, or classically defined echocardiographic findings of organ damage (i.e., left ventricular concentric remodelling and increased filling pressures).
| S-EPMC8087482 | biostudies-literature
Project description:The recent genome-wide analysis of carotid-femoral pulse wave velocity (PWV) identified a significant locus within the 14q32.2 gene desert. Gene regulatory elements for the transcriptional regulator B-cell CLL/lymphoma 11B (BCL11B) are within this locus and an attractive target for the gene association. We investigated the functional impact of these gene desert SNPs on BCL11B transcript in human aorta to characterize further its role in aortic stiffness. To do this, we used a large repository of aortic tissues (n = 185) from an organ transplant program and assessed ex vivo stiffness of the aortic rings. We tested association of three lead SNPs from the GWAS meta-analysis with ex vivo aortic stiffness and BCL11B aortic mRNA expression: rs1381289 and rs10782490 SNPs associated significantly with PWV and showed allele-specific differences in BCL11B mRNA. The risk alleles associated with lower BCL11B expression, suggesting a protective role for BCL11B. Despite strong association, we could not detect BCL11B protein in the human aorta. However, qPCR for CD markers showed that BCL11B transcript correlated strongly with markers for activated lymphocytes. Our data confirm the significance of the 14q32.2 region as a risk locus for aortic stiffness and an upstream regulator of BCL11B. The BCL11B transcript detected in the human aorta may reflect lymphocyte infiltration, suggesting that immune mechanisms contribute to the observed association of BCL11B with aortic stiffness.
| S-EPMC6189060 | biostudies-literature
Project description:Increased arterial stiffness and wave reflection have been identified as cardiovascular disease risk factors. In light of significant sex differences and the moderate heritability of vascular function measures, we hypothesized that variation in the genes coding for oestrogen receptors alpha (ESR1) and beta (ESR2) and aromatase (CYP19A1) is associated with aortic stiffness and pressure wave reflection as measured by non-invasive arterial tonometry. In all, 1261 unrelated Framingham Offspring Study participants who attended the seventh examination cycle (mean age 62+/-10 years, 52% women) and had arterial tonometry and genotyping data were included in the study. Analysis of covariance was used to assess the association of polymorphisms with forward wave amplitude, augmented pressure, augmentation index (AI), carotid-femoral pulse wave velocity and mean arterial pressure with adjustment for potential confounders. In the sex-pooled analysis, those homozygous for the minor allele at any of four ESR1 variants that were in strong linkage disequilibrium ((TA)(n), rs2077647, rs2234693 and rs9340799) had on an average 18% higher augmented pressure and 16% greater AI compared with carriers of one or two major alleles (P=0.0002-0.01). A similar magnitude of association was detected in those homozygous for the common allele at two ESR2 single-nucleotide polymorphisms (P=0.007-0.02). Our results are consistent with the hypothesis that variation in ESR1 and ESR2, but not CYP19A1, is associated with an increased wave reflection that may contribute to associations between these variants and adverse clinical events demonstrated earlier. Our findings will need to be replicated in additional cohorts.
| S-EPMC2746260 | biostudies-literature