The sodium chloride cotransporter (NCC) is essential for electrolyte balance, blood pressure regulation, and pathophysiology of hypertension as it mediates the reabsorption of ultrafiltered sodium in the renal distal convoluted tubule. Given its pivotal role in the maintenance of extracellular fluid volume, the NCC is regulated by a complex network of cellular pathways, which eventually results in either its phosphorylation, enhancing sodium and chloride ion absorption from urines, or dephosphorylation and ubiquitination, which conversely decrease NCC activity. Several factors could influence NCC function, including genetic alterations, hormonal stimuli, and pharmacological treatments. The NCC’s central role is also highlighted by several abnormalities resulting from genetic mutations in its gene and consequently in its structure, leading to dysregulation of blood pressure control. In the last decade, among other improvements, the acquisition of knowledge on the NCC and other renal ion channels has been favored by studies on extracellular vesicles (EVs). Dietary sodium and potassium intake are also implicated in the tuning of NCC activity. In this narrative review, we present the main cornerstones and recent evidence related to NCC control, focusing on the context of blood pressure pathophysiology, and promising new therapeutical approaches.

Lipoprotein(a) [Lp(a)] is a causal risk factor for coronary artery disease (CAD), with proposed prothrombotic properties besides proatherogenic effects. However, the association between Lp(a) and coagulation remains controversial so far. This study examined this relationship in subjects with or without angiographically documented CAD. Plasma levels of Lp(a) and coagulation biomarkers were assessed in clinically stable subjects undergoing elective coronary angiography. Subjects taking any anticoagulant therapy were excluded. The coagulation panel included coagulant activities of factors II, V, VII, VIII, IX, X, XI, and XII, von Willebrand factor antigen (vWF:Ag), thrombin generation assay (TGA), total tissue factor pathway inhibitor (TFPI), and activated factor VII-antithrombin (FVIIa-AT) complex. Lp(a) threshold values were defined according to the European Atherosclerosis Society consensus statement: normal 50 mg/dL. Complete laboratory data were available for 383 subjects (males 75.3%; mean age 68.2 ± 9.7 years): 65 subjects had normal coronary arteries, 51 subjects had coronary stenosis <50%, and 267 subjects had coronary stenosis ≥50%. A modest yet significant increase in FV coagulant activity (FV:C) from low to high Lp(a) plasma levels was found and confirmed after adjustment for potential confounding factors. No differences were observed for all the other coagulant activities, vWF:Ag, total TFPI, FVIIa-AT levels, or TGA parameters. In this pilot study, no major contribution of Lp(a) plasma levels was observed in modulating coagulation phenotype, as evaluated by multiple biomarkers. High Lp(a) plasma levels were associated with only a mild increase in FV:C.

Background/Objectives: Fatty acids (FAs) play crucial roles in human physiology, and their levels have been associated with hypertension, although with inconsistent findings. Primary Aldosteronism (PA), a common, often underdiagnosed form of secondary hypertension, carries a higher risk of organ damage compared to essential hypertension (EH). This study aimed to compare plasma FA profiles of patients with unilateral PA and EH and explore the impact of therapies. Methods: Participants were recruited at the Hypertension Unit of Verona University Hospital. PA diagnosis/subtype was confirmed according to guidelines. Blood samples were collected at enrollment and at follow-up (after treatment with a mineralocorticoid receptor antagonist (MRA) and adrenalectomy). Plasma long- and very-long-chain FAs were extracted and analyzed using gas chromatography. Results: Each sample was assessed for a panel of 19 selected FA species. Compared to EH (n = 60), PA patients (n = 22) exhibited lower plasma levels of behenic acid (p = 0.03), total monounsaturated fatty acids (p = 0.02), specifically palmitoleic (p = 0.005) and erucic acids (p = 0.02), and higher levels of ω6 polyunsaturated fatty acids (PUFAs, p = 0.02). Longitudinal analysis in PA patients showed that MRAs decreased total saturated FAs (p_ADJ = 0.01) and increased total PUFAs (p_ADJ = 0.006), and these changes were largely maintained even after adrenalectomy. Conclusions: This pilot study reveals significant alterations in the plasma FA profiles of PA patients compared to EH, suggesting a more prominent inflammatory state in PA. Both pharmacological and surgical interventions induced a positive shift in the FA profile of PA patients. These findings highlight the potential of FAs as biomarkers for PA risk stratification and may offer novel therapeutic opportunities.