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QiShenYiQi Pills Attenuates Ischemia/Reperfusion-Induced Cardiac Microvascular Hyperpermeability Implicating
Chun-Shui Pan1,2,3,4, Li Yan1,2,3,4, Se-Qi Lin5
1Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Insights
QiShenYiQi Pills (QSYQ) protect against ischemia/reperfusion (I/R) injury by reducing coronary microvascular hyperpermeability. QSYQ maintains endothelial junctions and basement membrane integrity through the Src/caveolin-1 and RhoA/ROCK/MLC pathways.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Coronary microvascular hyperpermeability exacerbates ischemia/reperfusion (I/R) injury.
- Limited effective strategies exist to mitigate this microvascular insult.
- Understanding the protective mechanisms against I/R-induced hyperpermeability is crucial.
Purpose of the Study:
- To investigate the protective effects of QiShenYiQi Pills (QSYQ) against cardiac I/R-induced microvascular hyperpermeability.
- To elucidate the underlying molecular mechanisms of QSYQ's action.
Main Methods:
- Rats underwent coronary artery occlusion followed by reperfusion, with QSYQ administration prior to ischemia.
- Human cardiac microvascular endothelial cells (HCMECs) were subjected to hypoxia/reoxygenation (H/R) with QSYQ treatment.
- Assessment of microvascular damage, albumin leakage, endothelial junctions, and signaling pathways (Src, caveolin-1, RhoA/ROCK/MLC, MMP-9, CTSS).
Main Results:
- QSYQ attenuated microvascular damage and albumin leakage in I/R injury.
- QSYQ preserved endothelial junctions and basement membrane integrity.
- In HCMECs, QSYQ protected the endothelial barrier from H/R, normalizing mitochondrial function and inhibiting key signaling molecules.
Conclusions:
- QiShenYiQi Pills (QSYQ) effectively prevent ischemia/reperfusion-induced cardiac microvascular hyperpermeability.
- The protective mechanism involves the modulation of Src/caveolin-1 and RhoA/ROCK/MLC signaling pathways.
- QSYQ demonstrates potential as a therapeutic agent for I/R injury.
Abstract:
Aims: Coronary microvascular hyperpermeability is an important contributor to ischemia or reperfusion (I/R) injury. However, the effective strategy for this insult remains limited. This study aimed to explore the protective effect of the compound Chinese medicine QiShenYiQi Pills (QSYQ) against coronary microvascular hyperpermeability after cardiac I/R with focusing on the underlying mechanism. Methods and Results: Male Sprague-Dawley rats under anesthesia were subjected to occlusion of left coronary anterior descending artery followed by reperfusion. QSYQ was administrated 90 min before ischemia initiation. Human cardiac microvascular endothelial cells (HCMECs) underwent hypoxia or reoxygenation (H/R) challenge with QSYQ administrated 1 h prior to hypoxia. QSYQ exhibited effects on attenuating microvascular damage and albumin leakage after I/R injury, showing a role in maintaining endothelial junctions, caveolae, and collagen in basement membrane (BM) of microvessels. Study using HCMECs disclosed that QSYQ protected endothelial barrier from impairment by H/R, attenuating the decline of respiratory chain complex I and ATP synthase, activation of Src/caveolin-1 and increase of RhoA/ROCK/p-MLC, MMP-9, and CTSS. PP2, a Src inhibitor, partially imitated the effect of QSYQ. Conclusions: The QSYQ was able to prevent I/R-induced cardiac microvascular hyperpermeability via a mechanism involving Src/caveolin-1 and RhoA/ROCK/MLC signaling.
