Cardiovascular Diseases (CVDs) are the leading cause of death globally. More than 17 million people die worldwide from CVD per year. There is considerable evidence suggesting that estrogen modulates cardiovascular physiology and function in both health and disease, and that it could potentially serve as a cardioprotective agent. The effects of estrogen on cardiovascular function are mediated by nuclear and membrane estrogen receptors (ERs), including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G-protein-coupled ER (GPR30 or GPER). Receptor binding in turn confers pleiotropic effects through both genomic and non-genomic signaling to maintain cardiovascular homeostasis. Each ER has been implicated in multiple pre-clinical cardiovascular disease models. This review will discuss current reports on the underlying molecular mechanisms of the ERs in regulating vascular pathology, with a special emphasis on hypertension, pulmonary hypertension, and atherosclerosis, as well as in regulating cardiac pathology, with a particular emphasis on ischemia/reperfusion injury, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction.

Rationale: Pulmonary hypertension (PH) is a rare but fatal disease characterized by elevated pulmonary pressures and vascular remodeling, leading to right ventricular failure and death. Recently, neuroinflammation has been suggested to be involved in the sympathetic activation in experimental PH. Whether PH is associated with neuroinflammation in the spinal cord has never been investigated. Methods/Results: PH was well-established in adult male Wistar rats 3-week after pulmonary endothelial toxin Monocrotaline (MCT) injection. Using the thoracic segments of the spinal cord, we found a 5-fold increase for the glial fibrillary acidic protein (GFAP) in PH rats compared to controls (p < 0.05). To further determine the region of the spinal cord where GFAP was expressed, we performed immunofluorescence and found a 3 to 3.5-fold increase of GFAP marker in the gray matter, and a 2 to 3-fold increase in the white matter in the spinal cord of PH rats compared to controls. This increase was due to PH (MCT vs. Control; p < 0.01), and there was no difference between the dorsal versus ventral region. PH rats also had an increase in the pro-inflammatory marker chemokine (C-C motif) ligand 3 (CCL3) protein expression (∼ 3-fold) and (2.8 to 4-fold, p < 0.01) in the white matter. Finally, angiogenesis was increased in PH rat spinal cords assessed by the adhesion molecule CD31 expression (1.5 to 2.3-fold, p < 0.01). Conclusion: We report for the first time evidence for neuroinflammation in the thoracic spinal cord of pulmonary hypertensive rats. The impact of spinal cord inflammation on cardiopulmonary function in PH remains elusive.

Purpose: The purpose of this study is to investigate demographic and hospital characteristics that predict hospital price transparency in the United States. Methods: We identified 6214 hospitals and extracted characteristics of each using the American Hospital Association Annual Survey, as well as cash prices for a representative selection of commonly performed procedures and visits from the Turquoise Health dataset. Descriptive statistics were used to determine compliance rates and price variation, and a Poisson regression model was used to calculate incidence rate ratios (IRR) and 95% confidence intervals (CI) for predictors of price transparency. Results: Price transparency compliance ranged from 13% to 49% of hospitals, and across-center ratios ranged from 244.8 to 4789.0. Number of hospital beds was marginally associated with price transparency for more services (IRR: 1.01 [95% CI: 1.01– 1.02]); in contrast, location in the Southern (IRR: 0.91 [95% CI: 0.87– 0.96]) or Western (IRR: 0.94 [95% CI: 0.90– 0.99]) regions of the US was associated with transparency for fewer services. Conclusion: Smaller hospitals as well as those located in the South and West regions were less likely to be compliant with the CMS mandate for price transparency for hospital standard charges. Additionally, the poor usability of price transparency directories on hospital websites limits information access and undermines transparency efforts.