AI Article Synopsis
- Chronic methamphetamine (METH) exposure is linked to high blood pressure (hypertension) and vascular remodeling, but the exact mechanisms are not fully understood.
- Researchers developed a mouse model to study METH's effects, discovering that the Sigma1 receptor (Sigmar1) plays a crucial role in hypertension and collagen buildup around blood vessels.
- The study suggests that targeting Sigmar1 could be a new treatment strategy for METH-induced hypertension and related vascular issues.
Article Abstract
Aim: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension.
Methods And Results: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-β/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells.
Conclusion: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-β/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.
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| http://dx.doi.org/10.1016/j.bbadis.2024.167284 | DOI Listing |
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