Jatrorrhizine inhibits Piezo1 activation and reduces vascular inflammation in endothelial cells.

Vascular inflammation is a common pathological basis underlying many cardiovascular diseases. As such, the treatment of vascular inflammation has attracted increasing attention. The Piezo1 pathway has long been shown to play an important role in the development of vascular inflammation. Jatrorrhizine (Jat) is an effective component of Rhizoma Coptidis. It is commonly used in the treatment of inflammatory diseases and is a potential drug for the treatment of vascular inflammation. However, its mechanism of action on vascular inflammation remains unclear, as is the effect of Jat on Piezo1. Therefore, we conducted a series of studies on the effect of jatrorrhizine on vascular inflammation in vivo and in vitro. In this study, the effect of Jat treatment on H2O2-induced endothelial cell inflammation was investigated in vitro, and the potential mechanism of Jat was explored. In in vivo experiments, we investigated the effect of jatrorrhizine on vascular inflammation induced by carotid artery ligation and its effect on the Piezo1 signaling pathway. We found that Jat could reduce the severity of carotid intimal hyperplasia and local vascular inflammation in mice. In the H2O2-induced inflammation model, cell proliferation and migration were significantly inhibited, and the expression of pro-inflammatory factors was reduced. Importantly, the addition of Jat to endothelial Piezo1 knockout did not produce further significant inhibition. We believe that the role of Jat in the treatment of vascular inflammation may be related to Piezo1. And we believe that Jat has great potential in the treatment of vascular inflammation and cardiovascular diseases.

Piezo1 in vascular remodeling of atherosclerosis and pulmonary arterial hypertension: A potential therapeutic target.

Vascular remodeling (VR) is a structural and functional change of blood vessels to adapt to the changes of internal and external environment. It is one of the common pathological features of many vascular proliferative diseases. The process of VR is mainly manifested in the changes of vascular wall structure and function, including intimal hyperplasia, thickening or thinning of media, fibrosis of adventitia, etc. These changes are also the pathological basis of aging and various cardiovascular diseases. Mechanical force is the basis of cardiovascular biomechanics, and the newly discovered mechanical sensitive ion channel Piezo1 is widely distributed in the whole cardiovascular system. Studies have confirmed that Piezo1, a mechanically sensitive ion channel, plays an important role in cardiovascular remodeling diseases. This article reviews the molecular mechanism of Piezo1 in atherosclerosis, hypertension and pulmonary hypertension, in order to provide a theoretical basis for the further study of vascular remodeling.

Inhibition of chemically and mechanically activated Piezo1 channels as a mechanism for ameliorating atherosclerosis with salvianolic acid B.

BACKGROUND AND PURPOSE: Salvianolic acid B (SalB) is effective for treating cardiovascular diseases. However, the molecular mechanisms underlying its therapeutic effects remain unclear. Mechanosensitive Piezo1 channels play important roles in vascular biology, although their pharmacological properties are poorly defined. Here, we aimed to identify novel Piezo1 inhibitors and gain insights into their mechanisms of action. EXPERIMENTAL APPROACH: Intracellular Ca2+ ions were measured in HUVECs, murine liver endothelial cells (MLECs), THP-1 and RAW264.7 cell lines and bone marrow-derived macrophages (BMDMs). Isometric tensions in mouse thoracic aorta were recorded. Shear-stress assays with HUVECs were conducted. Patch-clamp recordings with mechanical stimulation were performed with HUVECs in whole-cell mode. Foam cell formation was induced by treating BMDMs with oxidised LDL (oxLDL). Atherosclerotic plaque assays were performed with Ldlr-/- and Piezo1 genetically depleted mice on a high-fat diet. KEY RESULTS: Salvianolic acid B inhibited Yoda1-induced Ca2+ influx in HUVECs and MLECs. Similar results were observed in macrophage cell lines and BMDMs. Furthermore, we demonstrated that salvianolic acid B inhibited Yoda1- and mechanically activated currents. Salvianolic acid B suppressed Yoda1-induced aortic ring relaxation and inhibited HUVECs alignment in the direction of shear stress. Additionally, Yoda1 enhanced the formation of foam cells, which was reversed by salvianolic acid B. Salvianolic acid B also inhibited formation of atherosclerotic plaques and was insensitive to Piezo1 genetic depletion. CONCLUSION AND IMPLICATIONS: Our study provides novel mechanistic insights into the inhibitory role of salvianolic acid B against Piezo1 channels and improves our understanding of salvianolic acid B in preventing atherosclerotic lesions.