Epigenetic Regulation of Angiogenesis in Peripheral Artery Disease

Malhi, Naseeb Kaur; Southerland, Kevin W.; Lai, Li; Chen, Zhen Bouman

doi:10.14797/mdcvj.1294

Cited by 1 publication

(1 citation statement)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peripheral artery disease (PAD) is a common condition characterized by the narrowing or the blockage of the arteries, typically in the lower limbs, that leads to reduced blood flow and subsequent tissue ischaemia [ 1 , 2 , 3 ]. Given that such diseases represent a major health concern worldwide, an increasing number of studies have turned towards the profound investigation of the dynamic changes in tissue perfusion during acute hindlimb ischaemia (AHI) [ 4 , 5 , 6 ]. In this respect, pre-clinical imaging techniques seem to be promising tools to shed light on AHI-related pathophysiological processes, which may eventually open an avenue for the development of effective diagnostic and therapeutic strategies [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study

Farkasinszky,

Péliné,

Károlyi

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Background: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). Methods: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. Results: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. Conclusions: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.

show abstract