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The interaction of lead exposure and CCM3 defect plays an important role in regulating angiogenesis through eNOS/NO

Yi Sun1, Zhiqiang Zhao2, Haifeng Zhang3

  • 1Department of Health Toxicology, Sun Yat-sen University School of Public Health, Guangzhou, Guangdong, 510080, China; Department of Environmental Health and Occupational Medicine, Guilin Medical University School of Public Health, Guilin, Guangxi, 541004, China.

Environmental Toxicology and Pharmacology
|June 9, 2020
PubMed

Insights

Cerebral cavernous malformation 3 (CCM3) gene deficiency increases susceptibility to lead-induced abnormal vascular development. Nitric oxide (NO) release likely mediates these adverse effects on angiogenesis.

Area of Science:

  • Vascular biology
  • Toxicology
  • Developmental biology

Background:

  • Cerebral cavernous malformations (CCMs) are vascular abnormalities.
  • CCM3 gene is crucial for vascular development.
  • Lead exposure can disrupt vascular integrity.

Purpose of the Study:

  • Investigate nitric oxide (NO) role in CCM3 deficiency-induced angiogenesis.
  • Examine lead acetate (PbAc) effects on vascular development.
  • Elucidate the underlying molecular mechanisms.

Main Methods:

  • Whole mount immunofluorescent staining of retinal vessels in wild-type (WT) and CCM3+/- mice.
  • Isolation and treatment of brain microvascular endothelial cells (BMECs), HUVECs, and immortalized HUVECs (imHUVECs) with PbAc.
  • RT-PCR and Western blotting to analyze iNOS, eNOS, and VEGF gene expression.

Main Results:

  • Lead exposure and CCM3 deficiency impaired endothelial cell function, leading to abnormal angiogenesis and vascular remodeling.
  • Significant differences in eNOS and iNOS mRNA expression were observed in WT and CCM3+/- BMECs.
  • PbAc exposure increased eNOS and iNOS expression in imHUVECs (CCM3+/+ and CCM3-/-).

Conclusions:

  • CCM3 gene deficiency exacerbates lead-induced abnormal vascular development.
  • Nitric oxide (NO) release is implicated in the adverse effects of lead on angiogenesis in CCM3-deficient models.
  • These findings highlight the critical role of CCM3 in vascular health and response to environmental toxins.
Keywords:
AngiogenesisCCM3Endothelial cellLeadNitric oxide

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