The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.

Gastroesophageal reflux disease (GERD) is commonly seen in patients with chronic kidney disease (CKD), although data on the relationship between these conditions are still limited. We aimed to explore whether CKD is related to a higher prevalence of GERD and its complications. National Inpatient Sample data were used in this retrospective analysis, including 7,159,694 patients. Patients who had a diagnosis of GERD with and without CKD were compared with patients without GERD. Complications associated with GERD that were analyzed included Barrett’s esophagus and esophageal stricture. Risk factors of GERD were used for variable adjustment analysis. Different stages of CKD were evaluated in patients with and without GERD. Bivariate analyses were performed using the chi-squared test or Fisher exact test (2-tailed) for categorical variables as appropriate to assess the difference. There were significantly different demographic characteristics between GERD patients with and without CKD regarding age, sex, race, and other co-mobilities. Interestingly, a greater prevalence of GERD was seen in CKD patients (23.5%) compared to non-CKD patients (14.8%), and this increased prevalence was consistently seen in all CKD stages. CKD patients also had 1.70 higher odds of risk of having GERD compared with non-CKD after adjustment. The association between different stages of CKD and GERD showed a similar trend. Interestingly, patients with early-stage CKD were found to have a higher prevalence and odds of risk of esophageal stricture and Barrett’s esophagus than non-CKD patients. CKD is associated with a high prevalence of GERD and its complications.

Caveolin binding motif of Na/K-ATPase is essential for mammals and C. elegans organogenesis.

Background and Objective: Presenting chronic obstructive pulmonary disease (COPD) patients frequently report concurrent symptoms of gastroesophageal reflux disease (GERD). Few studies have shown a correlation between GERD and COPD. We aimed to examine the correlation between GERD and COPD as well as secondary related reflux complications, such as esophageal stricture, esophageal cancer, and Barrett’s esophagus. Methods: This population-based analysis included 7,159,694 patients. Patients diagnosed with GERD with and without COPD were compared to those without GERD. The enrollment of COPD included centrilobular and panlobular emphysema and chronic bronchitis. Risk factors of COPD or GERD were used for adjustment. Bivariate analyses were performed using the chi-squared test or Fisher exact test (2-tailed) for categorical variables as appropriate to assess the differences in the groups. Results: Our results showed that COPD patients had a significantly higher incidence of GERD compared to those without COPD (27.8% vs. 14.1%, p < 0.01). After adjustment of demographics and risk factors, COPD patients had a 1.407 times higher risk of developing non-erosive esophagitis (p < 0.01), 1.165 higher risk of erosive esophagitis (p < 0.01), 1.399 times higher risk of esophageal stricture (p < 0.01), 1.354 times higher risk of Barrett’s esophagus without dysplasia (p < 0.01), 1.327 times higher risk of Barrett’s esophagus with dysplasia, as well as 1.235 times higher risk of esophageal cancer than those without COPD. Conclusions: Based on the evidence from this study, there are sufficient data to provide convincing evidence of an association between COPD and GERD and its secondary reflux-related complications.

Patients with obstructive sleep apnea (OSA) commonly report gastroesophageal reflux disease (GERD) symptoms, and limited data suggest a relationship between OSA and GERD-related complications. To investigate this association, we performed a population-based analysis using National Inpatient Sample (NIS) data for 7,159,694 patients. After adjusting for risk factors, OSA patients had a significantly higher incidence of GERD (32.3%) compared to those without OSA (15.0%, p < 0.01). OSA patients also had a higher risk of developing GERD-related complications, including non-erosive esophagitis, erosive esophagitis, esophageal stricture, and Barrett’s esophagus with and without dysplasia. Therefore, our results emphasize the importance of early detection and management of GERD and its complications in patients with OSA, particularly those with additional risk factors such as obesity and smoking.

This study aimed to investigate the relationship between chronic kidney disease (CKD) and different gastric diseases by conducting a population-based retrospective analysis using National Inpatient Sample (NIS) data. A total of 7,159,694 patients diagnosed with gastric diseases with or without CKD were included, and the diagnoses of gastritis, gastric polyps, peptic ulcer disease (PUD), and Helicobacter pylori infection were based on ICD-10-CM codes. The study found a higher prevalence of gastritis and gastric polyps in patients with CKD compared to patients without CKD, especially in the late stages of CKD. After adjustment, patients with CKD also had a higher risk of developing these gastric diseases than patients without CKD. However, there was no significant association between all stages of CKD and PUD or Helicobacter pylori infection. These results underscored the importance of monitoring gastric health in patients with CKD.