Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy

Yolanda Garcia-Mesa; Roberto Cabo; Mario González-Gay; Jorge García-Piqueras; Eliseo Viña; Irene Martínez; Teresa Cobo; Olivia García-Suárez

doi:10.3389/fphys.2023.1243966

Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy

Front Physiol. 2023 Nov 20:14:1243966. doi: 10.3389/fphys.2023.1243966. eCollection 2023.

Authors

Yolanda Garcia-Mesa^{1

2}, Roberto Cabo^{1

2}, Mario González-Gay^{2

3}, Jorge García-Piqueras^{2

4}, Eliseo Viña^{1

2

5}, Irene Martínez^{2

6}, Teresa Cobo^{1

2

7

8}, Olivia García-Suárez^{1

2}

Affiliations

¹ Grupo SINPOS, Department of Cell Biology and Morphology, University of Oviedo, Oviedo, Spain.
² Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain.
³ Sercivio de Angiología y Cirugía Vascular, Fundación Hospital de Jove, Gijón, Spain.
⁴ Servicio de Anatomía, Histología y Neurociencias, Universidad Autonoma de Madrid, Spain.
⁵ Servicio de Cardiología, Unidad de Hemodinámica y Cardiología Intervencionista, Hospital de Cabueñes, Gijón, Spain.
⁶ Servicio de Cirugía Plástica y Reparadora, Fundación Hospital de Jove, Gijón, Spain.
⁷ Departamento de Cirugía y Especialidades Médico-Quirúrgicas, Universidad de Oviedo, Oviedo, Spain.
⁸ Instituto Asturiano de Odontología S.L, Oviedo, Spain.

Abstract

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes. Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (α-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction. Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency.

Keywords: DPN; Piezo; blood vessels; diabetic distal symmetrical polyneuropathy; painful and painless; skin.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was supported (in part) by the Intramural Research Program of the University of Oviedo (PAPI-20-EMERG-13).