Vascular Health Triad in Humans With Hypertension-Not the Usual Suspects

Area of Science:

• Cardiovascular Science
• Vascular Biology
• Human Physiology

Background:

• Hypertension (HTN) affects over a third of the US population and is a primary risk factor for cardiovascular disease (CVD).
• Endothelial dysfunction in resistance arteries initiates sub-clinical HTN, with inflammation and reactive oxygen/nitrogen species (ROS/RNS) playing synergistic roles.
• The interplay of inflammation, ROS/RNS, and vascular dysfunction, termed the vascular health triad, critically influences blood pressure regulation.

Purpose of the Study:

• To review the role of specific molecular targets, termed 'unusual suspects,' in the vascular health triad.
• To connect novel mechanistic insights into inflammation, ROS/RNS, and vascular dysfunction in human hypertension.
• To highlight potential therapeutic targets for managing blood pressure and preventing CVD.

Main Methods:

• Literature review of recent human studies focusing on molecular mechanisms of HTN.
• Analysis of the roles of inducible nitric oxide synthase, hydrogen peroxide, hydrogen sulfide, NF-κB, and nuclear factor activated T cells.
• Synthesis of data linking these targets to inflammation, ROS/RNS, and endothelial dysfunction.

Main Results:

• Inducible nitric oxide synthase, hydrogen peroxide, hydrogen sulfide, NF-κB, and nuclear factor activated T cells are implicated as key players in the vascular health triad.
• These 'unusual suspects' contribute to inflammation and oxidative stress, exacerbating endothelial dysfunction.
• Dysregulation of these pathways directly impacts blood pressure control in individuals with or at risk for HTN.

Conclusions:

• The vascular health triad, involving inflammation, ROS/RNS, and endothelial dysfunction, is central to HTN pathogenesis.
• Novel molecular targets like NF-κB and hydrogen sulfide offer new avenues for understanding and treating hypertension.
• Further research into these 'unusual suspects' is crucial for developing effective CVD prevention strategies.