[Tissue consequence of renin-angiotensin system activation]

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Endocrinology

Context:

• The renin-angiotensin system (RAS) is compartmentalized, with distinct functions in circulating blood and local tissue environments.
• Renin and its substrate can move between compartments, but angiotensin peptides primarily act where generated.
• Tissue-bound renin interacts with specific receptors, influencing local RAS activity.

Purpose:

• To elucidate the compartmentalized actions of the renin-angiotensin system (RAS) and its role in pathological vascular remodeling.
• To detail the molecular mechanisms underlying angiotensin II's effects in different cellular compartments.
• To explore the involvement of RAS in hypertension, diabetes, and atherosclerosis.

Summary:

• Angiotensin II binding to AT1 receptors triggers immediate calcium responses, hypertrophy, and late-stage inflammation and coagulation, mediated by reactive oxygen species and NF-κB.
• In vivo, renin tissue binding and enzyme induction are key to RAS-driven vascular remodeling.
• Interstitial angiotensin II targets vascular smooth muscle cells and fibroblasts, while circulating angiotensin II affects endothelial cells and leukocytes. Angiotensin II promotes vascular hypertrophy in hypertension, induces TGF-β in diabetes-related fibrosis, and contributes to aneurysm formation in atherosclerosis.

Impact:

• Understanding RAS compartmentalization is crucial for developing targeted therapies for cardiovascular diseases.
• The findings highlight angiotensin II's central role in mediating pathological vascular remodeling, inflammation, and fibrosis.
• While angiotensin II antagonists show promise in animal models, their efficacy in human cardiovascular diseases requires further investigation.