The mechanical properties of single cells play important roles in regulating cell-matrix interactions, potentially influencing the process of mechanotransduction. Recent studies also suggest that cellular mechanical properties may provide novel biological markers, or "biomarkers," of cell phenotype, reflecting specific changes that occur with disease, differentiation, or cellular transformation. Of particular interest in recent years has been the identification of such biomarkers that can be used to determine specific phenotypic characteristics of stem cells that separate them from primary, differentiated cells. The goal of this study was to determine the elastic and viscoelastic properties of three primary cell types of mesenchymal lineage (chondrocytes, osteoblasts, and adipocytes) and to test the hypothesis that primary differentiated cells exhibit distinct mechanical properties compared to adult stem cells (adipose-derived or bone marrow-derived mesenchymal stem cells). In an adherent, spread configuration, chondrocytes, osteoblasts, and adipocytes all exhibited significantly different mechanical properties, with osteoblasts being stiffer than chondrocytes and both being stiffer than adipocytes. Adipose-derived and mesenchymal stem cells exhibited similar properties to each other, but were mechanically distinct from primary cells, particularly when comparing a ratio of elastic to relaxed moduli. These findings will help more accurately model the cellular mechanical environment in mesenchymal tissues, which could assist in describing injury thresholds and disease progression or even determining the influence of mechanical loading for tissue engineering efforts. Furthermore, the identification of mechanical properties distinct to stem cells could result in more successful sorting procedures to enrich multipotent progenitor cell populations.
Background Food deserts (FD), neighborhoods defined as low-income areas with low access to healthy food, are a public health concern. We evaluated the impact of living in FD on cardiovascular risk factors and subclinical cardiovascular disease (CVD) with the hypothesis that people living in FD will have an unfavorable CVD risk profile. We further assessed whether the impact of FD on these measures is driven by area income, individual household income or area access to healthy food. Methods and Results We studied 1421 subjects residing in the Atlanta metropolitan area who participated in the META-Health (n = 712) and the Predictive Health (n = 709) studies. Participants’ zip codes were entered into the United States Food Access Research Atlas for FD status. Demographic data, metabolic profiles, high-sensitivity C-reactive protein (hs-CRP) levels, oxidative stress markers (glutathione and cystine) and arterial stiffness were evaluated. Mean age was 49.4 years, 38.5% male and 36.6% Black. Compared to those not living in FD, subjects living in FD (n=187, 13.2%) had a higher prevalence of hypertension and smoking, higher BMI, fasting glucose and 10-year risk for CVD. They also had higher hs-CRP (p=0.014), higher central augmentation index (p=0.015), and lower glutathione level (p=0.003), indicative of increased oxidative stress. Area income and individual income, rather than food access, were associated with CVD risk measures. In a multivariate analysis that included food access, area income and individual income, both low-income area and low individual household income were independent predictors of a higher 10-year risk for CVD. Only low individual income was an independent predictor of higher hs-CRP and augmentation index. Conclusions Although living in FD is associated with a higher burden of cardiovascular risk factors and preclinical indices of CVD, these associations are mainly driven by area income and individual income rather than access to healthy food.
Background Oxidative stress (OS) may be a key mechanism underlying the development of atrial fibrillation (AF) in experimental studies, but data in humans remain limited. Objective Systemic OS can be estimated by measurements of circulating levels of the aminothiols including glutathione, cysteine, and their oxidized products. We tested the hypothesis that the redox potentials of glutathione (EhGSH) and cysteine will be associated with prevalent and incident AF. Methods Plasma levels of aminothiols were measured in 1439 patients undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident AF. Multivariate logistic regression and Cox regression models were used to determine whether OS markers were independent predictors of prevalent and incident AF after adjustment for traditional risk factors, heart failure, coronary artery disease, and high-sensitivity C-reactive protein level. Results For each 10% increase in EhGSH, the odds of prevalent AF was 30% higher (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.1–1.7; P = .02) and 90% higher (OR 1.9; 95% CI 1.3–2.7; P = .004) when the median was used as a cutoff. The EhGSH level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3– 12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1–2.7; P = .03). Each 10% increase in EhGSH level was associated with a 40% increase in the risk of incident AF (hazard ratio 1.4; 95% CI 1.1– 1.7; P = .01). Conclusion Increased OS measured by the redox potentials of glutathione is associated with prevalent and incident AF. Therapies that modulate OS need to be investigated to treat and prevent AF.
BackgroundBeing unmarried is associated with decreased survival in the general population. Whether married, divorced, separated, widowed, or never‐married status affects outcomes in patients with cardiovascular disease has not been well characterized.Methods and ResultsA prospective cohort (inception period 2003–2015) of 6051 patients (mean age 63 years, 64% male, 23% black) undergoing cardiac catheterization for suspected or confirmed coronary artery disease was followed for a median of 3.7 years (interquartile range: 1.7–6.7 years). Marital status was stratified as married (n=4088) versus unmarried (n=1963), which included those who were never married (n=451), divorced or separated (n=842), or widowed (n=670). The relationship between marital status and primary outcome of cardiovascular death and myocardial infarction was examined using Cox regression models adjusted for clinical characteristics. There were 1085 (18%) deaths from all causes, 688 (11%) cardiovascular‐related deaths, and 272 (4.5%) incident myocardial infarction events. Compared with married participants, being unmarried was associated with higher risk of all‐cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.06–1.47), cardiovascular death (HR: 1.45; 95% CI, 1.18–1.78), and cardiovascular death or myocardial infarction (HR: 1.52; 95% CI, 1.27–1.83). Compared with married participants, the increase in cardiovascular death or myocardial infarction was similar for the participants who were divorced or separated (HR: 1.41; 95% CI, 1.10–1.81), widowed (HR: 1.71; 95% CI, 1.32–2.20), or never married (HR: 1.40; 95% CI, 0.97–2.03). The findings persisted after adjustment for medications and other socioeconomic factors.ConclusionsMarital status is independently associated with cardiovascular outcomes in patients with or at high risk of cardiovascular disease, with higher mortality in the unmarried population. The mechanisms responsible for this increased risk require further study.
BackgroundThe associations between high‐sensitivity troponin I (hsTnI) levels and coronary artery disease (CAD) severity and progression remain unclear. We investigated whether there is an association between hsTnI and angiographic severity and progression of CAD and whether the predictive value of hsTnI level for incident cardiovascular outcomes is independent of CAD severity.Methods and ResultsIn 3087 patients (aged 63±12 years, 64% men) undergoing cardiac catheterization without evidence of acute myocardial infarction, the severity of CAD was calculated by the number of major coronary arteries with ≥50% stenosis and the Gensini score. CAD progression was assessed in a subset of 717 patients who had undergone ≥2 coronary angiograms >3 months before enrollment. Patients were followed up for incident all‐cause mortality and incident cardiovascular events. Of the total population, 11% had normal angiograms, 23% had nonobstructive CAD, 20% had 1‐vessel CAD, 20% had 2‐vessel CAD, and 26% had 3‐vessel CAD. After adjusting for age, sex, race, body mass index, smoking, hypertension, diabetes mellitus history, and renal function, hsTnI levels were independently associated with the severity of CAD measured by the Gensini score (log 2 ß=0.31; 95% confidence interval, 0.18–0.44; P<0.001) and with CAD progression (log 2 ß=0.36; 95% confidence interval, 0.14–0.58; P=0.001). hsTnI level was also a significant predictor of incident death, cardiovascular death, myocardial infarction, revascularization, and cardiac hospitalizations, independent of the aforementioned covariates and CAD severity.ConclusionsHigher hsTnI levels are associated with the underlying burden of coronary atherosclerosis, more rapid progression of CAD, and higher risk of all‐cause mortality and incident cardiovascular events. Whether more aggressive treatment aimed at reducing hsTnI levels can modulate disease progression requires further investigation.
Background Endogenous regenerative capacity, assessed as circulating progenitor cell (PC) numbers, is an independent predictor of adverse outcomes in patients with cardiovascular disease. However, their predictive role in heart failure (HF) remains controversial. We assessed the relationship between the number of circulating PCs and the etiology and severity of HF and their impact on incident HF events. Methods and Results We recruited 2049 adults of which 651 had heart failure diagnosis. PCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, CD133, VEGFR2 and CXCR4 epitopes. PC subsets were lower in number in HF and after adjustment for clinical characteristics in multivariable analyses, a low CD34+ and CD34+/CXCR+ cell count remained independently associated with a diagnosis of HF (P<0.01). PCs levels were not significantly different in reduced [HFrEF] vs preserved [HFpEF] ejection fraction patients. In 514 subjects with HF, there were 98 (19.1%) all cause deaths during a 2.2 ± 1.5 year follow-up. In a Cox regression model adjusting for clinical variables, hematopoietic-enriched PCs (CD34+, CD34+/CD133+ and CD34+/CXCR4+) were independent predictors of all-cause death (Hazard ratio [HR] 2.0, 1.6, 1.6-fold higher mortality, respectively, P<0.03) among HF patients. Endothelial-enriched PCs (CD34+/VEGF+) were independent predictors of mortality in patients with HFpEF only (HR=5.0, P=0.001). Conclusions PC levels are lower in patients with HF and lower PC counts are strongly and independently predictive of mortality. Strategies to increase PCs and exogenous stem cell therapies designed to improve regenerative capacity in HF, especially in HFpEF need to be further explored.
IMPORTANCE Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown.OBJECTIVE To investigate whether therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves exercise capacity in patients with intermittent claudication. DESIGN, SETTING, AND PARTICIPANTSIn a phase 2 double-blind, placebo-controlled study, 159 patients (median [SD] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, Georgia, between January 2010 and July 2012.INTERVENTIONS Participants were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 μg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily. MAIN OUTCOMES AND MEASURESThe primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating PC levels, ankle brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores. RESULTSOf the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% CI, 67 to 151]) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14 to 98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, −6 to 112], P = .08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7 to 16.1) vs 4.8 (95% CI, −0.1 to 9.6), with a mean difference in change for GM-CSF vs placebo of 7.5 (95% CI, 1.0 to 14.0; P = .03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4 to 18.7) vs 4.8 (95% CI, −0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2 to 15.7], P = .047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups.CONCLUSIONS AND RELEVANCE Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up. The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication.
Introduction Despite the growing interest in place as a determinant of health, areas that promote rather than reduce cardiovascular disease (CVD) in blacks are understudied. We performed an ecologic analysis to identify areas with high levels of CVD resilience and risk among blacks from a large southern, US metropolitan area. Methods We obtained census tract–level rates of cardiovascular deaths, emergency department (ED) visits, and hospitalizations for black adults aged 35 to 64 from 2010 through 2014 for the Atlanta, Georgia, metropolitan area. Census tracts with substantially lower rates of cardiovascular events on the basis of neighborhood socioeconomic status were identified as resilient and those with higher rates were identified as at risk. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) of being classified as an at-risk versus resilient tract for differences in census-derived measures. Results We identified 106 resilient and 121 at-risk census tracts, which differed in the rates per 5,000 person years of cardiovascular outcomes (mortality, 8.13 vs 13.81; ED visits, 32.25 vs 146.3; hospitalizations, 26.69 vs 130.0), despite similarities in their median black income ($46,123 vs $45,306). Tracts with a higher percentage of residents aged 65 or older (odds ratio [OR], 2.29; 95% CI, 1.41–3.85 per 5% increment) and those with incomes less than 200% of the federal poverty level (OR, 1.19; 95% CI, 1.02–1.39 per 5% increment) and greater Gini index (OR, 1.56; 95% CI, 1.19– 2.07 per 0.05 increment) were more likely to be classified as at risk than resilient neighborhoods. Discussion Despite matching on median income level, at-risk neighborhoods for CVD among black populations were associated with a higher prevalence of socioeconomic indicators of inequality than resilient neighborhoods.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.