Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure

Rachel A. Dee, Kevin D. Mangum, Xue Bai, Christopher P Mack, Joan M Taylor

Research output: Contribution to journalReview article

Abstract

The prevalence of high blood pressure (also known as hypertension) has steadily increased over the last few decades. Known as a silent killer, hypertension increases the risk for cardiovascular disease and can lead to stroke, heart attack, kidney failure and associated sequela. While numerous hypertensive therapies are currently available, it is estimated that only half of medicated patients exhibit blood pressure control. This signifies the need for a better understanding of the underlying cause of disease and for more effective therapies. While blood pressure homeostasis is very complex and involves the integrated control of multiple body systems, smooth muscle contractility and arterial resistance are important contributors. Strong evidence from pre-clinical animal models and genome-wide association studies indicate that smooth muscle contraction and BP homeostasis are governed by the small GTPase RhoA and its downstream target, Rho kinase. In this review, we summarize the signaling pathways and regulators that impart tight spatial-temporal control of RhoA activity in smooth muscle cells and discuss current therapeutic strategies to target these RhoA pathway components. We also discuss known allelic variations in the RhoA pathway and consider how these polymorphisms may affect genetic risk for hypertension and its clinical manifestations.

LanguageEnglish (US)
Pages121-134
Number of pages14
JournalPharmacology and Therapeutics
Volume193
DOIs
StatePublished - Jan 1 2019

Fingerprint

Blood Pressure
Hypertension
Smooth Muscle
Homeostasis
rho-Associated Kinases
Monomeric GTP-Binding Proteins
Genome-Wide Association Study
Therapeutics
Muscle Contraction
Smooth Muscle Myocytes
Renal Insufficiency
Cardiovascular Diseases
Animal Models
Stroke
Myocardial Infarction

Keywords

  • Blood pressure
  • GTPase activating protein (GAP)
  • Guanine nucleotide exchange factor (GEF)
  • Rho Kinase (ROCK)
  • RhoA
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure. / Dee, Rachel A.; Mangum, Kevin D.; Bai, Xue; Mack, Christopher P; Taylor, Joan M.

In: Pharmacology and Therapeutics, Vol. 193, 01.01.2019, p. 121-134.

Research output: Contribution to journalReview article

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