Piezo & Cardiovascular Diseases

Piezo & Cardiovascular Diseases

David J. Beech, Antreas C. Kalli. Force Sensing by Piezo Channels in Cardiovascular Health and Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 2021

Piezo1 and Piezo2 ion channels - pressure & electronics

- Ca2+-permeable non-selective cationic channels

- Non-specifically inhibited by Gd3+

- Large & unusual structures

- Reliably activated by mechanical forces & Yuda1 activation without shear forces

- Genetic evidence: important but not crucial to human life

Piezo1:

- Mechano-sensing ion channel expressed in endothelial cells

- Transmembrane, trimer

- Force sensing

- inverted dome shape indentation of the membrane: energy storage & membrane tension

- Tension sensitivity

- Multiple biochemical pathways: cardiovascular, kidney, skeletal muscle, and pancreas

Homozygote Piezo1 global knockout

- mice embryonic lethal, failed vascular maturation

- Essential in mice but not in humans? / compensation?

- Technical limitations: critical variation in the timing of Tie2-mediated recombination

Dichotomy - due to Ca2+-non-selective cationic channels in non-excitable cells

- Vasodilation and Vasoconstriction

- Specific disruption: elevated resting systolic BP and blunt elevated diastolic and systolic BP caused by whole-body physical activity

Piezo2:

- Even larger inverted dome shape

- Neural & Sensory roles

- Suggested expression in endothelial cells & key roles in blood pressure regulation

Piezo1 & Piezo2:

- Conditional 1 or 2 disruption in ganglia: no effect on BP or baroreceptor reflex

- Double knockout abolished reflex, ↓HR, ↑systolic BP & its variability

- Critical baroreceptor pressure sensors & important to acute blood pressure regulation

- Disruption of only one may not reveal significance

Literature Searches:

Dominique Douguet, Amanda Patel, Aimin Xu, Paul Vanhoutte, Eric Honoré. Piezo ion channels in cardiovascular mechanobiology. Trends in Pharmacological Sciences, Elsevier, 2019, ff10.1016/j.tips.2019.10.002ff. ffhal-02386137

Pharmacological modulators of Piezo

The mechanotransduction of blood pressure by HEIMO EHMKE

The Role of PIEZO2 in Human Mechanosensation