EDN1-Endothelin 1 |Elisa - Clia - Antibody - Protein

Background:

Endothelin-1 (ET-1) is a peptide hormone belonging to the endothelin family. It plays a crucial role in regulating blood vessel contraction and dilation, thereby influencing blood pressure and blood flow throughout the body. Endothelin-1 is primarily produced by endothelial cells, It is also produced by other cell types, including vascular smooth muscle cells, cardiomyocytes, and certain inflammatory cells.Endothelin-1 acts as a potent vasoconstrictor, meaning it causes blood vessels to narrow, leading to an increase in blood pressure. Dysregulation of endothelin-1 signaling is associated with several cardiovascular disorders, including hypertension, atherosclerosis, coronary artery disease, and pulmonary hypertension. Elevated levels of endothelin-1 have been observed in individuals with these conditions, contributing to their pathogenesis. Endothelin-1 is able to bind to specific receptors on target cells known as endothelin receptors. There are two main types of endothelin receptors: endothelin receptor type A (ETA) and endothelin receptor type B (ETB). ETA receptors are primarily located on vascular smooth muscle cells and mediate vasoconstriction, while ETB receptors are found on both endothelial cells and smooth muscle cells and have diverse functions, including vasodilation and clearance of endothelin-1 from the bloodstream.

Protein Structure:

• Primary Structure: EDN1 is synthesized as a precursor, preproendothelin-1 (prepro-EDN1), which undergoes proteolytic cleavage to form proendothelin-1 (big-EDN1). Big-EDN1 is then further cleaved by endothelin-converting enzyme (ECE) to produce the active 21-amino acid peptide, endothelin-1.
• Secondary and Tertiary Structure: EDN1 has a characteristic structure with two disulfide bridges that create a unique conformation essential for its binding to endothelin receptors.

Classification and Subtypes:

Endothelin peptides, including EDN1, are classified based on their amino acid sequence and biological activity. EDN1, EDN2, and EDN3 are encoded by separate genes and exhibit distinct tissue distribution and physiological roles. EDN1 is the most potent and widely studied isoform due to its significant impact on vascular function.

Function and Biological Significance:

• Vasoconstriction: EDN1 is a powerful vasoconstrictor, contributing to the regulation of vascular tone and systemic blood pressure. It acts on vascular smooth muscle cells to induce contraction.
• Cell Proliferation and Survival: Beyond its vascular effects, EDN1 promotes cell proliferation, migration, and survival, particularly in smooth muscle cells and cardiomyocytes. This has implications for vascular remodeling and cardiac hypertrophy.
• Inflammation and Fibrosis: EDN1 is involved in inflammatory and fibrotic processes. It stimulates the production of pro-inflammatory cytokines and fibrotic markers, contributing to conditions such as pulmonary fibrosis and chronic kidney disease.
• Neurotransmission: In the nervous system, EDN1 plays a role in neurotransmission and has been implicated in pain modulation.

Interactions:

• Endothelin Receptors: EDN1 exerts its effects by binding to endothelin receptors, primarily endothelin receptor type A (ETA) and type B (ETB). ETA receptors are predominantly located on vascular smooth muscle cells and mediate vasoconstriction, while ETB receptors are found on endothelial cells and are involved in vasodilation and clearance of endothelin.
• Other Signaling Pathways: EDN1 interacts with various signaling molecules and pathways, including nitric oxide (NO), angiotensin II, and reactive oxygen species (ROS), modulating vascular function and inflammatory responses.

Clinical Issues:

• Hypertension: Elevated levels of EDN1 are associated with hypertension due to its potent vasoconstrictive effects.
• Heart Failure: Increased EDN1 activity contributes to the pathophysiology of heart failure by promoting cardiac hypertrophy, fibrosis, and reduced cardiac output.
• Pulmonary Arterial Hypertension (PAH): EDN1 plays a significant role in PAH, leading to increased pulmonary vascular resistance and right heart failure.
• Renal Diseases: EDN1 contributes to the progression of chronic kidney disease and acute kidney injury through its effects on renal hemodynamics and fibrosis.
• Cancer: EDN1 has been implicated in cancer progression due to its role in cell proliferation, migration, and angiogenesis. Elevated EDN1 levels are found in various cancers, including prostate, ovarian, and colorectal cancers.

Summary:

Endothelin 1 (EDN1) is a critical peptide in the regulation of vascular tone and blood pressure, with significant roles in cell proliferation, inflammation, and fibrosis. It interacts with endothelin receptors to mediate its diverse biological effects. Dysregulation of the endothelin system, particularly EDN1, is implicated in various cardiovascular, renal, and inflammatory diseases, as well as cancer. Understanding the molecular mechanisms and clinical implications of EDN1 provides insights into potential therapeutic targets for these conditions.