Browsing by Author "Jayachandran, Muthuvel (7004632107)"

Objective To measure carotid artery intima-media thickness (CIMT), a marker of subclinical atherosclerosis, in postmenopausal women with and without histories of preeclampsia and to synthesize these results with those from prior studies of CIMT performed 10 or more years after preeclamptic pregnancies. Patients and Methods Forty women (median age, 59 years) with histories of preeclampsia and 40 with histories of normotensive pregnancy (confirmed by medical record review) were selected from women who resided and gave birth in Olmsted County, Minnesota, between January 1, 1976, and December 31, 1982. The participants were identified and recruited in 2014-2015, and CIMT was measured by B-mode ultrasonography. Meta-analysis included CIMT studies that were performed 10 or more years after preeclamptic pregnancies and which were identified through PubMed, EMBASE, and Web of Science. Heterogeneity was assessed using the I2 statistic. Standardized mean difference was used as a measure of effect size. Results Carotid artery intima-media thickness, expressed as a median (interquartile range), was greater in the preeclamptic than in the normotensive group (0.80 mm [0.75-0.85 mm] vs 0.73 mm [0.70-0.78]; P=.004); the odds of having CIMT higher than threshold (0.77 mm) was statistically significant after adjusting for confounding factors (odds ratio, 3.17; 95% CI, 1.10-9.14). A meta-analysis of 10 studies conducted 10 or more years post partum included 813 women with and 2874 without histories of preeclampsia. Carotid artery intima-media thickness was greater among women with histories of preeclampsia, with a standardized mean difference of 0.18 and 95% CI of 0.05 to 0.30 mm (P=.004). Conclusion Among women with histories of preeclampsia, CIMT may identify those with subclinical atherosclerosis, thus offering an opportunity for early intervention. © 2017 Mayo Foundation for Medical Education and Research

Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocytespecific proteinswould be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and a1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of HbF in podocyte injury was studied in pregnant rabbits. Compared with urine from women with normotensive pregnancies, urine from women with preeclamptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podocin+ EVs-to-nephrin+ EVs ratio) and increased nephrinuria, both of which correlated with proteinuria. Plasma levels of hemopexin, which were decreased in women with preeclampsia, negatively correlated with proteinuria, urinary podocin+ EVs-to-nephrin+ EVs ratio, and nephrinuria. Administration of HbF to pregnant rabbits increased the number of urinary EVs of podocyte origin. These findings provide evidence that urinary EVs are reflective of preeclampsia-related altered podocyte protein expression. Furthermore, renal injury in preeclampsia associated with an elevated urinary podocin+ EVs-to-nephrin+ EVs ratio and may be mediated by prolonged exposure to cellfree HbF. © 2017 by the American Society of Nephrology.

BACKGROUND: Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. METHODS: We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. RESULTS: Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho (P=0.018); increased leptin (P=0.016) and leptin/adiponectin ratio (P=0.027), and increased extracellular vesicles positive for tissue factor (P=0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment (P=0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women (P=0.003). CONCLUSIONS: Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia. © 2024 Lippincott Williams and Wilkins. All rights reserved.