The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus

Abstract

Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents “mandatory damage” in the development of microvascular complications and only “introductory damage” in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.

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“…Accumulating data suggest an increasing trend in the incidence of type 2 diabetes mellitus, especially in younger people [23,24]. Notably, microvascular complications of diabetes mellitus represent a major threat to public health [25,26]. Simultaneously, DKD is a common microvascular complication of diabetes.…”

Recent Advances in Biomolecular Patho-Mechanistic Pathways behind the Development and Progression of Diabetic Neuropathy

“…hexosamine pathway [48], poly ADP-ribose polymerase (PARP) [49], Advanced glycation end-product (AGE) [50], oxidative stress [51], mitochondrial dysfunction [52], Wnt pathway [53], Hh pathway [54], mitogen-activated protein kinase (MAPK) signaling pathway [55], impaired insulin signaling, Glycogen synthase kinase 3 (GSK3) [56,57], Nuclear factor kappa B (NF-κB) [58], Cyclooxygenase (COX), Lectin-like oxidized low-density lipoprotein (LDL) receptor (LOX) [59], Interleukin (IL) [60], neurotrophic and cellular signaling, tumor necrosis factor (TNF)-α [61], autophagy, satellite glia cells, Schwann cells [62]. Different biochemical mechanisms associated with nerve and neurovascular injury have demonstrated that oxidative stress could modify the typical operation of metabolic mechanisms implicated in DN.…”

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