Altered Plasma Membrane Lipid Composition in Hypertensive Neutrophils Impacts Epithelial Sodium Channel (ENaC) Endocytosis.

Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval. This study assessed the structural lipid composition of neutrophil plasma membranes from HTN patients along with the expression patterns of key elements regulating ENaC at the plasma membrane. Our findings suggest alterations in microdomain structure and SGK1 kinase activity, which could prolong ENaC presence on the plasma membrane. Additionally, we propose that the proteasomal and lysosomal degradation pathways are insufficient to diminish ENaC presence at the plasma membrane in HTN. These results highlight the importance of understanding ENaC retrieval mechanisms and suggest that targeting these mechanisms could provide insights for developing drugs to prevent and treat HTN.

Occurrence of perfluorinated carboxylic acids in Mexico City's wastewater: A monitoring study in the sewerage and a mega wastewater treatment plant.

An analytical method based on liquid chromatography coupled to mass spectrometry was validated to quantify five perfluorinated carboxylic acids (PFCA) namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), and perfluoroundecanoic acid (PFUnA), in wastewater produced in a megacity. Sampling was performed on a monthly basis, obtaining samples from the undergrounded sewerage system and the main open-air canal transporting wastewater out the city. Steady levels of the sum of the target PFCA (Æ©PFCA) were determined on both sites through the study: 419.4 ± 24.3 ng L-1 in undergrounded sewage and 591.1 ± 39 ng L-1 in the open-air canal. Short-chain PFCA (PFBA, PFHxA, and PFHpA) were abundant, while concentrations of PFOA and PFUnA remained lower in both sampling sites. The open-air canal was transected in four sampling points, which were sampled throughout the monitoring campaign, finding that furtive discharges of municipal and industrial wastewater increased the levels of short-chain PFCA, while those of PFOA and PFUnA were depleted. Relevant concentrations of PFBA (176.9 ± 3.3 ng L-1), PFHxA (133.4 ± 2.5 ng L-1), PFHpA (116.6 ± 3.9 ng L-1), PFOA (133.1 ± 3.5 ng L-1), and PFUnA (23.5 ± 6.5 ng L-1) were found 60 km downstream, where the wastewater transported by the open-air canal is used in irrigation. A fraction of sewage is treated in a conventional wastewater treatment plant. The concentration of short-chain PFCA increased in effluent, adding extra loads of PFBA, PFHxA, and PFHpA to the environment.

Alterations to the contents of plasma membrane structural lipids are associated with structural changes and compartmentalization in platelets in hypertension.

Arterial hypertension (HTN) can lead to serious organ damage. Several mechanisms have been implicated in the pathogenesis of HTN including constitutive activation of platelets, which increases the risk of aggregation and clot formation. We recently demonstrated the plasma membranes of platelets from patients with HTN exhibit modified structural and physicochemical properties; Raman and Fourier transform infrared by attenuated total reflectance (FTIR-ATR) spectroscopy also indicated lipid content and protein structure alterations. This study aimed to precisely quantify the constituents of the main structural phospholipids and cholesterol in the plasma membranes of platelets from patients with HTN and normotensive individuals. We also assessed the consequence of these alterations on platelet structure and function. Liquid chromatography coupled to triple quadrupole mass spectrometry revealed the plasma membranes of HTN platelets contained less cholesterol and phosphatidylcholine, more phosphatidylserine and phosphatidylethanolamine and had similar sphingosine contents. Atomic force microscopy revealed HTN platelets exhibited increased surface roughness and more pleats. Transmission electron microscopy revealed diminution of the internal membranous structures in HTN platelets. Our findings strongly suggest plasma membrane lipid content alterations-including cholesterol depletion-occur in HTN, and these alterations may induce morphological and physiological abnormalities that participate in the functional changes associated with hypertension.

Alterations to plasma membrane lipid contents affect the biophysical properties of erythrocytes from individuals with hypertension.

Genetic and environmental factors may contribute to high blood pressure, which is termed essential hypertension. Hypertension is a major independent risk factor for cardiovascular disease, stroke and renal failure; thus, elucidation of the etiopathology of hypertension merits further research. We recently reported that the platelets and neutrophils of patients with hypertension exhibit altered biophysical characteristics. In the present study, we assessed whether the major structural elements of erythrocyte plasma membranes are altered in individuals with hypertension. We compared the phospholipid (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingosine) and cholesterol contents of erythrocytes from individuals with hypertension (HTN) and healthy individuals (HI) using LC/MS-MS. HTN erythrocytes contained higher phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine contents and a lower cholesterol content than HI erythrocytes. Furthermore, atomic force microscopy revealed important morphological changes in HTN erythrocytes, which reflected the increased membrane fragility and fluidity and higher levels of oxidative stress observed in HTN erythrocytes using spectrophotofluorometry, flow cytometry and spectrometry. This study reveals that alterations to the lipid contents of erythrocyte plasma membranes occur in hypertension, and these alterations in lipid composition result in morphological and physiological abnormalities that modify the dynamic properties of erythrocytes and contribute to the pathophysiology of hypertension.