Epigenetic basis of diabetic vasculopathy

Figures

• 

  Figure 1. Major biochemical and cellular pathways underlying endothelial dysfunction leading to vascular complications associated with T2DM. Chronic hyperglycemia activates different pathways involved in leading to endothelial dysfunction in T2DM subjects result in decreased activity of eNOS and increased mitochondrial ROS overproduction. This will bring up a pro-inflammatory environment by activation of several mediators which alter the endothelial epigenome and followed by aberrant transcription of genes regulating inflammatory response, macrophage infiltration, apoptosis and fibrosis resulting in diabetic vascular complications. Reproduced with permission from Elsevier. Following original report was credited: Dhawan et al. (51).

• 

  Figure 2. Schematic diagram shows the role of hyperglycemia induced epigenetic mechanisms in metabolic memory and diabetic endothelial dysfunction. DNMTs, DNA methyltransferases; HMTs, histone methyltransferases; HATs, histone acetyltransferases; eNOS, endothelial nitric oxide synthase; NO, nitric oxide, AGE, advanced glycation end products; PKC, protein kinase; NF-κB, nuclear factor-κB.

• 

  Figure 3. High glucose induces epigenetic reprogramming in endothelial cells and influences genes that are associated with its (dys)functions. DNA methylation and demethylation, histone modifications, miRNAs and lncRNAs regulate the activity of various genes related to angiogenesis and stimulate pathophysiological pathways leading to an inflammatory response and subsequently to vascular complications. Reproduced with permission from Elsevier. Following original report was credited: Dhawan et al. (51 ).

• 

  Figure 4. Role of miRNAs in endothelial cell phenotype, functions and vascular disease and their direct targets. MicroRNAs involved in: (A) angiogenesis, (B) vascular inflammation and atherosclerotic vascular disease, (C) vascular tone and endothelial cell barrier, and (D) secreted microRNAs and biomarkers. Reproduced under the terms of the Creative Commons CC BY license published by Elsevier. The following original report is credited: Chamorro-Jorganes et al. (105).

• 

  Figure 5. Optical windows and imaging chambers for skin and adipose tissue visualization by IVM. Non-invasive methods include (A) ear pinna imaging and (B) foot-pad imaging. A semi-invasive method (C) includes the dorsal skinfold chamber, which requires the surgical implantation of two titanium or polymer frames that can hold a ring with a glass coverslip through which imaging is performed. An invasive method is the generation of a skin flap (D), whereby a skin flap is generated, exposing a large imaging area. This procedure is invasive and terminal. A less commonly used method for IVM imaging is the skin flank (E) which requires the generation of an incision at a dorsolateral location, and either direct imaging or mounting on a stainless-steel disc for stable image acquisition. For adipose tissue imaging, various types of windows exist to visualize various depots (marked by X). To image the perigonadal adipose tissue, a terminal lower abdominal window (F) was generated. Reproduced under the terms of the Creative Commons CC BY license published by John Wiley and sons. The following original report is credited: De Niz et al. (152).

• 

  Figure 6. Intravital labeling for two-photon microscopic imaging of adult mouse skin vasculature. (A) Texas Red 40 KDa dextran marked the perfused vasculature and Rhodamine-123 marked the cytoplasm of cells present nearby the vasculature containing mitochondria. Scale bar = 80 µm. (B) Using Imaris software the 3-dimensional vessel structure was reconstructed from a region of interest (ROI) from panel (A) Grey color represent second-harmonic generation (SHG) indicative of collagen in the skin tissue.