Clinical Application of Epithelial Sodium Channel (ENaC) as a Biomarker for Arterial Hypertension

Abstract

Arterial hypertension (HTN) is a global public health concern and an important risk factor for cardiovascular diseases and renal failure. We previously reported overexpression of ENaC on the plasma membrane of human platelets is a hallmark of HTN. In this double-blinded study of an open population (n = 167), we evaluated the sensitivity and specificity of a diagnostic assay based on gold nanoparticles (AuNPs) conjugated to an antibody against epithelial sodium channel (ENaC) expressed on platelets, which is detected using a fluorescent anti-ENaC secondary antibody and spectrofluorometry. Using the cutoff value for the AuNP-anti-ENaC assay, we confirmed the diagnosis for 62.1% of patients with clinical HTN and detected 59.7% of patients had previously undiagnosed HTN. Although some shortcomings in terms of accurately discriminating healthy individuals and patients with HTN still need to be resolved, we propose this AuNP-anti-ENaC assay could be used for initial screening and early diagnosis to critically improve opportune clinical management of HTN.

Classification and application of metal-based nanoantioxidants in medicine and healthcare

“…Gold nanorods serving as surface-enhanced Raman scattering probes have demonstrated sensitivity for the early detection of ICAM-1, a significant signal for screening atherosclerosis, particularly in macrophages. Moreover, AuNPs with different sizes and shapes exhibit the capability to inhibit angiogenesis, especially at 20 nm size [ 178 , 186 ]. In 2022, García-Rubio and colleagues introduced a novel diagnostic approach to differentiate between normal blood pressure and hypertension.…”

“…In 2022, García-Rubio and colleagues introduced a novel diagnostic approach to differentiate between normal blood pressure and hypertension. This method involves the conjugation of gold nanoparticles (AuNPs) with an anti-epithelial sodium channel (ENaC), known as a marker for arterial hypertension found in membrane platelets [ 186 ]. Beyond nanotechnology, the field has witnessed developments in metallic biomaterials for vascular tissue engineering.…”

Role of epithelial sodium channel-related inflammation in human diseases

“…Several phospholipids have been reported to have a regulatory effect on the ENaC. Phosphatidylinositol ( 4 , 5 )-bisphosphate (PIP2) and phosphatidylinositol ( 3 – 5 )-triphosphate (PIP3) have a direct positive regulatory role on the C-terminal of β and γENaC ( 49 ). Thus, many substances that have a regulatory effect on PIP2 and PIP3 can indirectly modulate ENaC activity, such as phospholipase C ( 49 ), myristoylated alanine-rich C-kinase ( 50 ), and phospholipase β3 ( 51 ).…”

“…The most important function of the ENaC is to maintain the physical and cellular Na + homeostasis by mediating Na + reabsorption in the kidneys, colon, lungs, and skin. ENaC dysfunction is associated with a variety of diseases: ENaC overexpression in the kidneys manifests as increased blood volume and hypertension ( 3 ), impaired ENaC in the colon manifests as inflammation of intestinal mucosa and diarrhea ( 4 ), and dysfunction of the ENaC in the lungs leads to pneumonia and respiratory distress ( 5 ). The expression and activity of the ENaC are regulated by a variety of factors; hormones such as renin-angiotensin-aldosterone system (RAAS), insulin, and vasopressin can maintain Na + metabolic homeostasis by regulating the ENaC.…”

The Epithelial Sodium Channel—An Underestimated Drug Target

“…For this purpose, gold nanoparticles were conjugated to an antibody against ENaC. In 59.7% of patients with an undiagnosed HTN, an increased blood pressure could be detected, so that an application of a refined version of this assay for initial screening and early diagnosis of HTN is recommended [171].…”