Enhanced neointimal fibroblast, myofibroblast content and altered extracellular matrix composition: Implications in the progression of human peripheral artery restenosis

Ramanathan, Krishnan; Purushothaman, K-Raman; Purushothaman, Meerarani; Turnbull, Irene C.; Tarricone, Arthur; Vasquez, Miguel; Jain, Sachin; Baber, Usman; Lascano, Rheoneil A.; Kini, Annapoorna; Sharma, Samin K.; Moreno, Pedro R.

doi:10.1016/j.atherosclerosis.2016.06.046

Cited by 21 publications

(13 citation statements)

References 44 publications

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“…In a similar manner, photonic emissions from collagens are generally associated with hydroxylysyl-pyridinoline and lysyl-pyridinoline groups that are affected by agedependent polymerization of monomeric chains and cross links [62]. In the normal arterial wall, collagen type I and Coll 3A1 are the main collagens in the media and adventitia while arterial injury alters the balance between TGF-β1 and these two types of collagen [63][64][65].…”

Section: Discussionmentioning

confidence: 96%

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Molony

King

Luca

et al. 2020

Preprint

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Background: A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening, lipid retention and plaque formation, yet their origin remains controversial. The ability to discriminate heterogeneous populations of cells in the context of various disease processes is of potential clinical and diagnostic value. Methods:The feasibility of multivariate analysis of single cell photonics as a discriminator of cell phenotype was assessed using label-free optical multi-parameter interrogation of single cells on a novel Lab-on-a-Disk (LoaD) platform before myogenic differentiation of a series of multipotent stem cells in vitro, and the cellular heterogeneity within vascular lesions in vivo, was determined using supervised machine learning and validated by genetic lineage tracing in vivo.Findings: Single cell photonics were of sufficient coverage, specificity, and quality to discriminate various disparate cell phenotypes in vitro and normal medial SMCs from SMClike cells following injury ex vivo, in addition to distinguishing myogenic differentiation of a series of multipotent stem cells in vitro. Supervised machine learning of these photonic datasets supported genetic lineage tracing analysis and identified the presence of S100β + stem-derived myogenic progeny within vascular lesions, in part, due to upregulation of Coll 3A1 and elastin.Interpretation: Disease-relevant photonic signatures reflect cell type and differentiation state and may have important predictive value as a phenotypic discriminator for vascular disease. Research in contextEvidence before this study: Cardiovascular disease (CVD), the leading cause of death and disability world-wide is characterized by pathological structural changes to the blood vessel wall. Pathologic observations in humans vessels confirm that early 'transitional' lesions enriched with SMC-like cells are routinely present in atherosclerotic-prone regions of arteries during pathologic intimal thickening, prior to lipid retention, and the appearance of a atherosclerotic plaque. Lineage tracing and single cell RNA sequence analysis (scRNA-seq) analysis has provided compelling evidence for the involvement of differentiated medial SMC and adventitial/medial progenitors derived from SMCs in progressing intimal thickening.Despite these insights, the putative role of resident vascular stem cells that do not originate from medial SMCs in promoting intimal thickening remains controversial. Light as a diagnostic and prognostic tool has several advantages including high sensitivity, non-destructive measurement, small or even non-invasive analysis and low limits of detection for early detection of disease phenotypes. In combination with microfluidics, photonics enables real time measurement of single cells in very small sample volumes. To accompany these photonic platforms, deep learning, a subset of supervised machine learning based primarily on artificial neural network geometries, has rapidly grown as a predictive method t...

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Section: Discussionmentioning

confidence: 96%

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Molony

King

Luca

et al. 2020

Preprint

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“…However, changes in the concentration of MMPs have been previously assessed in patients undergoing revascularisation of arterial districts other than peripheral limb, such as coronary arteries or carotid vessels . An increase in tissue inflammatory cytokines (TNF‐α and IL‐6) after rabbit common carotid artery injury suggesting their mutual role in promoting the restenotic process has been reported, and an increase of IL‐6 in restenotic plaques of patients affected with PAD has been also described …”

Section: Discussionmentioning

confidence: 99%

“…30 An increase in tissue inflammatory cytokines (TNF-α and IL-6) after rabbit common carotid artery injury suggesting their mutual role in promoting the restenotic process has been reported, 31 and an increase of IL-6 in restenotic plaques of patients affected with PAD has been also described. 32 We left all foot amputations open because of the extremely complex foot trauma and advanced arterial disease. It is possible that NPWT may have exerted a beneficial effect in the healing process in this clinically difficult setting.…”

Section: Healing Process In Trauma Patientsmentioning

confidence: 99%

Inflammatory biomarkers, vascular procedures of lower limbs, and wound healing

Sapienza

Mingoli

Borrelli

et al. 2019

International Wound Journal

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Abnormal, persistent inflammation after bypass surgery could prevent healing of an ischaemic foot lesion. In 37 patients with peripheral arterial disease (PAD) (Rutherford Grade III Category 5) who underwent infrapopliteal vein graft and midfoot amputation, plasma levels of fibrinogen, C‐reactive protein (CRP), interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), and matrix metalloproteinase‐2 and ‐9 (MMP‐2 and MMP‐9) were determined preoperatively and during the follow up. Nine patients without clinical and Doppler evidence of arterial disease, who underwent post‐traumatic midfoot primary amputation, were included in the experiment group, and 15 age‐matched healthy volunteers served as control. In patients who had midfoot amputation for trauma, all wounds healed. Seven (19%) wounds in patients with an occluded graft healed, and five (13%) required major amputation because of a non‐healing wound. Time required for complete healing of the lesion was similar between trauma and PAD patients (8 ± 2 months vs 11 ± 6, respectively, P = NS). Univariate analysis demonstrated that, in PAD patients, the postoperative high levels of TNF‐α, IL‐6, and MMP‐2 and ‐9 were predictive for wound healing failure at 3, 6, and 9 months (P < 0.05), respectively. Furthermore, the subgroup of patients who experienced occlusion of the vein graft during follow up had a significant increase of MMP‐2, ‐9, IL‐6, and TNF‐α at 3, 6, and 9 months (P < 0.05), respectively. Monitoring inflammatory markers allows the determination of patients at risk of healing failure of midfoot amputation after distal revascularisation and might predict the fate of the vein graft.

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“…Restenosis severely limits the overall efficacy of these interventions and can occur in up to 80% of patients. The process involves a complex cascade of reactions that result in luminal narrowing through a combination of neointimal hyperplasia and constrictive remodeling [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Photodynamic therapy for atherosclerosis. The potential of indocyanine green

Houthoofd¹,

Vuylsteke

Mordon

et al. 2020

Photodiagnosis and Photodynamic Therapy

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The aim of this article is to summarize and review the use of photodynamic therapy for the treatment of atherosclerotic plaque and the prevention of intimal hyperplasia. Different photosensitizers are discussed and more specific the role of indocyanine green as a potential photosensitizer. Methods: Literature search with focus on the use of photodynamic therapy in atherosclerosis, the mechanism of action and the different photosensitizers for photodynamic therapy. Results: In-vitro and in-vivo studies confirm the use of photodynamic therapy for the treatment of atherosclerosis and the prevention of restenosis. Non-specific accumulation of photosensitizer and thus phototoxicity, remains an important problem. Indocyanine green is a photosensitizer with features in favor of photodynamic therapy. The results of photodynamic therapy with indocyanine green point towards the potential of indocyanine green as a photosensitizer in photodynamic therapy for atherosclerosis. Conclusion: Photodynamic therapy is a promising tool for atherosclerosis. Many of the studied photosensitizers have toxic effects. Indocyanine green might be a good photosensitizer for the use of photodynamic therapy in atherosclerosis. These data justify further research to the use of indocyanine green as a photosensitizer in the treatment of atherosclerotic plaque both de novo or in restenotic lesions.

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Enhanced neointimal fibroblast, myofibroblast content and altered extracellular matrix composition: Implications in the progression of human peripheral artery restenosis

Cited by 21 publications

References 44 publications

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Inflammatory biomarkers, vascular procedures of lower limbs, and wound healing

Photodynamic therapy for atherosclerosis. The potential of indocyanine green

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