INTRODUCTION: Specialized pro-resolving lipid mediators (SPM) such as resolvin-D1 (RvD1) act to resolve vascular inflammation and may guard against the progression of restenosis following cardiovascular interventions. Stimulating synthesis of these mediators directly in vascular cells may increase their local availability, and thus, protect against restenotic injury. However, the ability of endothelial (EC) and vascular smooth muscle cells (VSMC) to produce SPMs from their polyunsaturated fatty acid precursor decosahexaenoic acid (DHA) via lipoxygenase (LO) enzymatic transformation remains unknown. We sought to determine whether vascular cells produce SPMs from DHA and, if they do, how inflammation and mechanical injury of the vasculature alter biosynthesis. METHODS: Primary cultures of human saphenous vein endothelial and smooth muscle cells were treated with DHA in cell culture media (+ 10% serum) for 4h-24h. Freshly dissected rabbit aorta was incubated intact or following gentle endothelial denudation in cell culture media (+10% serum) with or without DHA for 48h. SPM levels in media were quantified by LC-MS/MS and ELISA and lipoxygenase expression and localization were assessed by western blotting and immunofluorescence staining, respectively. RESULTS: EC and SMC receiving media without DHA did not synthesize SPMs within the detection limits of the assay, whereas DHA treatment produced 17-HDHA, 14-HDHA, Mar1, RvD5, RvD2, and a dose and time-dependent increase in RvD1 production in EC (10.1 ±1.0 pg for 1000nM at 24h) and SMC (7.4 ± 0.2 pg for 1000nM at 24h). Intact rabbit aorta incubated in DHA+ media produced 0.24 ± 0.05 pg RvD1/mg tissue whereas aorta incubated in DHA− media produced 0.13 ± 0.007 pg RvD1/mg tissue. Moreover, EC-denuded aortas produced less RvD1/mg tissue than intact aortas. 5-LO was expressed in both cell types, however DHA induced 5-LO expression in EC (1.3 fold -DHA) but not in SMC. DHA promoted a nuclear to cytoplasmic shift of 5-LO in both EC and SMC. Finally, TNF-α stimulated an increase in RvD1 production in EC. CONCLUSIONS: Human vascular cells and rabbit vascular tissue can biosynthesize SPMs de novo from their precursor DHA, signifying a new source of SPMs in the vasculature.

Vascular access dysfunction is a cause of morbidity and mortality in chronic kidney disease (CKD) patients that require hemodialysis. The major cause of vascular access failure is venous stenosis due to neointimal hyperplasia (NH). Vascular smooth muscle cells (VSMC) are critical for the development of NH lesions, as they have the ability to modulate their phenotype from a "contractile" to a "synthetic" phenotype in the presence of uremia, through the regulation of sensor genes for uremia danger signals and VSMC-specific differentiation genes. Recent research indicates that Caspase-1 (casp-1) activation plays an essential role in sensing metabolic danger signal-associated molecular patterns and initiating vascular inflammation. Carbamylated LDL, a uremic toxin that has been shown to be found in higher levels in patients with CKD and in CKD murine models when compared to controls, and could play a role in casp-1 activation. Therefore, the goal of this project is to examine the role of cLDL/CKD-driven casp-1 activation in VSMC and CKD-related NH. We have established a CKD mouse model and published on CKD-associated vascular remodeling. We exposed wild type and caspase-1 knockout mice to our CKD model, analyzed and quantified the NH lesion formed. We also examined in vitro and ex-vivo changes in VSMC-specific differentiation genes when exposed to uremic serum and cLDL, in the presence or absence of caspase-1 inhibitor. We found that CKD serum induces with casp-1 activation and phenotypic changes in VSMCs from a "contractile" to a "synthetic" phenotype, which are reversed with casp-1 inhibition. In an ex-vivo model using relative quantification we found that VSMC contractile markers α -Actin, Calponin, SM-22, and Smoothelin gene expression of CKD mouse carotid VSMC were higher in casp-1 knockout mice when compared to wild-type (1.40, 1.28, 1.22, 1.41 respectively). Also using an in-vivo model, relative quantification of α-actin decreased from 1.0 to 0.329 when VSMCs were exposed to uremic serum and but increased back to 0.588 when Caspase-1 inhibitor is added. The relative quantification of Calponin also decreased from 1.0 to 0.394 when exposed to uremic serum and increased back to 0.601 with caspase-1 inhibitor. We also found that caspase-1 deficiency significantly reversed CKD-related vascular remodeling in casp-1 knockout mice and reduced NH volume by 50% from 1,440,023in wild-type mice to 71,069 µm2 in casp-1 knockouts (p-value 0.002). This evidence provides evidence that casp-1 plays a critical role in NH formation. Furthermore our results provide a novel insight over the therapeutic potential of casp-1 inhibitors for CKD induced NH and other inflammation induced vascular remodeling. / Public Health

Vascular stents have become a standard for treating atherosclerosis due to distinct advantages in trauma and cost with other surgical techniques. Unfortunately, the therapy is hindered by the risk of a new blockage (termed restenosis) developing in the treated artery. Clinical studies have indicated that stent design is a major risk factor for restenosis, with failure rates varying from 20 to 40% for bare metal stents. Subsequently, there has been a significant effort devoted to reducing failure rates by covering stents in polymer coatings in which anti-proliferative drugs are embedded, however complications have arisen (e.g. incomplete endothelization, lack of success in peripheral arteries, lack of long-term follow-up studies) that have limited the success of this technology. It has been thought that restenosis is directly related to the mechanical conditions that vascular stents create. Moreover, it has been hypothesized that stents that induce higher non-physiologic stresses result in a more aggressive pathobiological response that can lead to restenosis development. In this study, a combination of computational modeling and in vivo analysis were conducted to investigate the artery stent-induced wall stresses, and subsequent biological inflammatory response. In particular, variations in stent design were investigated as a means of examining specific stent design criteria that minimize the mechanical impact of stenting. Collectively, these data indicate that stent designs that subject the artery wall to higher stress values result in significantly more neointimal tissue proliferation, therefore, confirming the aforementioned hypothesis. Moreover, this work provides valuable insight into the role that biomechanics can play in improving the success rate of this percutaneous therapy and overall patient care.

Objetivo: Avaliar se a administração sistêmica de cilostazol reduz a hiperplasia neointimal nas artérias ilíacas de suínos submetidas a angioplastia com cateter balão. Métodos: O trabalho foi desenvolvido na Unidade de Experimentação Animal do Hospital de Clínicas de Porto Alegre. Vinte suínos foram submetidos a angioplastia com cateter balão 6 x 40 mm na artéria ilíaca comum direita, guiada por ultrassonografia com Doppler. Os animais foram randomizados em dois grupos: grupo 1 (n = 10), no qual foi administrado cilostazol 50 mg em duas doses diárias, e grupo 2 (n = 10), considerado controle. Após 30 dias, os animais foram sacrificados, e as artérias ilíacas preparadas para análise histológica. Os cortes histológicos foram digitalizados e analisados por morfometria digital. A análise estatística foi realizada com o teste t de Student e o de Mann-Whitney. Resultados: Comparando as artérias ilíacas submetidas a angioplastia com as não submetidas a angioplastia, houve hiperplasia neointimal significativa (0,228 versus 0,119 mm2; p = 0,0001). Nas artérias submetidas a angioplastia, não houve diferença entre o grupo 1 (cilostazol) e o grupo 2 (controle) na área do lúmen (2,277 versus 2,575 mm2; p = 0,08), área da íntima (0,219 versus 0,237 mm2; p = 0,64), área da média (2,262 versus 2,393 mm2; p = 0,53) e no percentual de obstrução neointimal (8,857 versus 9,257 %; p = 0,82). Conclusão: O uso de cilostazol 50 mg em duas doses diárias não reduziu a hiperplasia neointimal em artérias ilíacas de suínos submetidas a angioplastia com cateter balão. / Objective: To evaluate whether systemic administration of cilostazol reduces neointimal hyperplasia in the iliac arteries of pigs after balloon angioplasty. Methods: This study was conducted in the Experimental Animal Unit of Hospital de Clínicas de Porto Alegre, Brazil. Twenty pigs underwent angioplasty of the right common iliac artery under Doppler ultrasound guidance using 6x40-mm balloon catheters. The animals were randomized to one of two groups: group 1 (n = 10) received 50 mg cilostazol in two doses a day; and group 2 (n = 10) was the control group. After 30 days, the animals were killed and their iliac arteries were prepared for histological analysis. Histological images were digitalized and analyzed using digital morphometry. The Student t and the Mann-Whitney tests were used for statistical analyses. Results: Iliac arteries that underwent angioplasty had significantly more neointimal hyperplasia than those with no angioplasty (0.228 versus 0.119 mm2; p = 0.0001) Group 1 (cilostazol) and 2 (control) had no significant differences in lumen (2.277 versus 2.575 mm2; p = 0.08), intima (0.219 versus 0.237 mm2; p = 0.64) or media (2.262 versus 2.393 mm2; p = 0.53) area, or in percentage of neointimal obstruction (8.857 versus 9.257 %; p = 0.82). Conclusion: The use of 50 mg cilostazol in two doses a day did not reduce neointimal hyperplasia in iliac arteries of pigs that underwent balloon angioplasty.

Objetivo: Avaliar se a administração sistêmica de cilostazol reduz a hiperplasia neointimal nas artérias ilíacas de suínos submetidas a angioplastia com cateter balão. Métodos: O trabalho foi desenvolvido na Unidade de Experimentação Animal do Hospital de Clínicas de Porto Alegre. Vinte suínos foram submetidos a angioplastia com cateter balão 6 x 40 mm na artéria ilíaca comum direita, guiada por ultrassonografia com Doppler. Os animais foram randomizados em dois grupos: grupo 1 (n = 10), no qual foi administrado cilostazol 50 mg em duas doses diárias, e grupo 2 (n = 10), considerado controle. Após 30 dias, os animais foram sacrificados, e as artérias ilíacas preparadas para análise histológica. Os cortes histológicos foram digitalizados e analisados por morfometria digital. A análise estatística foi realizada com o teste t de Student e o de Mann-Whitney. Resultados: Comparando as artérias ilíacas submetidas a angioplastia com as não submetidas a angioplastia, houve hiperplasia neointimal significativa (0,228 versus 0,119 mm2; p = 0,0001). Nas artérias submetidas a angioplastia, não houve diferença entre o grupo 1 (cilostazol) e o grupo 2 (controle) na área do lúmen (2,277 versus 2,575 mm2; p = 0,08), área da íntima (0,219 versus 0,237 mm2; p = 0,64), área da média (2,262 versus 2,393 mm2; p = 0,53) e no percentual de obstrução neointimal (8,857 versus 9,257 %; p = 0,82). Conclusão: O uso de cilostazol 50 mg em duas doses diárias não reduziu a hiperplasia neointimal em artérias ilíacas de suínos submetidas a angioplastia com cateter balão. / Objective: To evaluate whether systemic administration of cilostazol reduces neointimal hyperplasia in the iliac arteries of pigs after balloon angioplasty. Methods: This study was conducted in the Experimental Animal Unit of Hospital de Clínicas de Porto Alegre, Brazil. Twenty pigs underwent angioplasty of the right common iliac artery under Doppler ultrasound guidance using 6x40-mm balloon catheters. The animals were randomized to one of two groups: group 1 (n = 10) received 50 mg cilostazol in two doses a day; and group 2 (n = 10) was the control group. After 30 days, the animals were killed and their iliac arteries were prepared for histological analysis. Histological images were digitalized and analyzed using digital morphometry. The Student t and the Mann-Whitney tests were used for statistical analyses. Results: Iliac arteries that underwent angioplasty had significantly more neointimal hyperplasia than those with no angioplasty (0.228 versus 0.119 mm2; p = 0.0001) Group 1 (cilostazol) and 2 (control) had no significant differences in lumen (2.277 versus 2.575 mm2; p = 0.08), intima (0.219 versus 0.237 mm2; p = 0.64) or media (2.262 versus 2.393 mm2; p = 0.53) area, or in percentage of neointimal obstruction (8.857 versus 9.257 %; p = 0.82). Conclusion: The use of 50 mg cilostazol in two doses a day did not reduce neointimal hyperplasia in iliac arteries of pigs that underwent balloon angioplasty.

Objetivo: Avaliar se a administração sistêmica de cilostazol reduz a hiperplasia neointimal nas artérias ilíacas de suínos submetidas a angioplastia com cateter balão. Métodos: O trabalho foi desenvolvido na Unidade de Experimentação Animal do Hospital de Clínicas de Porto Alegre. Vinte suínos foram submetidos a angioplastia com cateter balão 6 x 40 mm na artéria ilíaca comum direita, guiada por ultrassonografia com Doppler. Os animais foram randomizados em dois grupos: grupo 1 (n = 10), no qual foi administrado cilostazol 50 mg em duas doses diárias, e grupo 2 (n = 10), considerado controle. Após 30 dias, os animais foram sacrificados, e as artérias ilíacas preparadas para análise histológica. Os cortes histológicos foram digitalizados e analisados por morfometria digital. A análise estatística foi realizada com o teste t de Student e o de Mann-Whitney. Resultados: Comparando as artérias ilíacas submetidas a angioplastia com as não submetidas a angioplastia, houve hiperplasia neointimal significativa (0,228 versus 0,119 mm2; p = 0,0001). Nas artérias submetidas a angioplastia, não houve diferença entre o grupo 1 (cilostazol) e o grupo 2 (controle) na área do lúmen (2,277 versus 2,575 mm2; p = 0,08), área da íntima (0,219 versus 0,237 mm2; p = 0,64), área da média (2,262 versus 2,393 mm2; p = 0,53) e no percentual de obstrução neointimal (8,857 versus 9,257 %; p = 0,82). Conclusão: O uso de cilostazol 50 mg em duas doses diárias não reduziu a hiperplasia neointimal em artérias ilíacas de suínos submetidas a angioplastia com cateter balão. / Objective: To evaluate whether systemic administration of cilostazol reduces neointimal hyperplasia in the iliac arteries of pigs after balloon angioplasty. Methods: This study was conducted in the Experimental Animal Unit of Hospital de Clínicas de Porto Alegre, Brazil. Twenty pigs underwent angioplasty of the right common iliac artery under Doppler ultrasound guidance using 6x40-mm balloon catheters. The animals were randomized to one of two groups: group 1 (n = 10) received 50 mg cilostazol in two doses a day; and group 2 (n = 10) was the control group. After 30 days, the animals were killed and their iliac arteries were prepared for histological analysis. Histological images were digitalized and analyzed using digital morphometry. The Student t and the Mann-Whitney tests were used for statistical analyses. Results: Iliac arteries that underwent angioplasty had significantly more neointimal hyperplasia than those with no angioplasty (0.228 versus 0.119 mm2; p = 0.0001) Group 1 (cilostazol) and 2 (control) had no significant differences in lumen (2.277 versus 2.575 mm2; p = 0.08), intima (0.219 versus 0.237 mm2; p = 0.64) or media (2.262 versus 2.393 mm2; p = 0.53) area, or in percentage of neointimal obstruction (8.857 versus 9.257 %; p = 0.82). Conclusion: The use of 50 mg cilostazol in two doses a day did not reduce neointimal hyperplasia in iliac arteries of pigs that underwent balloon angioplasty.

No description available.

No description available.

Neointimal hyperplasia (NIH) is a cardiovascular disease characterised by increased smooth muscle cell (SMC) inflammation and proliferation. Suppressor of cytokine signalling 3 (SOCS3) limits Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in vascular remodelling but is limited by its short biological half-life. Therefore, mutation of all 9 Lys residues that are potential sites of ubiquitylation to Arg should produce a mutated SOCS3 resistant to ubiquitin-mediated proteasomal degradation (“Lys-less” SOCS3). This study hypothesise that enhancing SOCS3 stability and limiting JAK/STAT signalling may provide sustained inhibition of the vascular remodelling in NIH. Lentiviral transduction of WT and Lys-less SOCS3 in human saphenous vein (HSVSMCs) was highly efficient after 48 hours (>97%) and was sustained over 2 weeks. Lys-less SOCS3 was resistant to ubiquitylation contrary to WT-transduced HSVECs, and Lys-less SOCS3 was more stable (t1/2=4h) than WT (t1/2<4h) (n=6, P<0.001) in HSVSMCs. In HSVSMCs, both Lys-less SOCS3 and WT inhibited sIL-6Rα/IL-6 mediated STAT3 activation but not extracellular signal regulated protein kinase 1/2 (ERK1/2) by 80±7% (Lys-lessSOCS3/pSTAT3) and 74±6% (WT/pSTAT3) (n=3, P<0.05) and similarly inhibited PDGF-mediated STAT3 activation but not ERK1/2 by 67±17% (Lys-less SOCS3/pSTAT3) and 72±18% (WT/pSTAT3) (n=3, P<0.05). Functionally, Lys-less SOCS3 and WT were equivalent in inhibiting sIL-6Rα/IL-6 and PDGF-induced proliferation, whilst having no effects on PDGF-induced migration in HSVSMCs. Lys-less SOCS3 can be successfully transduced into primary HSVSMCs. It is more stable than WT yet retains its functional ability to ameliorate pro-inflammatory signalling and SMC proliferation, making it an attractive option for developing treatment of NIH. / University of Botswana

Η οπτική συνεκτική τομογραφία με τη χρήση συχνοτήτων ( FD-OCT) είναι μια ενδαγγειακή απεικονιστική μέθοδος που χρησιμοποιεί εγγύς στο υπέρυθρο φως, για να παράγει υψηλής ανάλυσης εικόνες του τοιχώματος του αυλού του αγγείου. Όπως και στην τεχνολογία υπερήχων, εκπέμπεται φωτεινή ενέργεια η οποία ανακλάται και εξασθενεί, σύμφωνα με την υφή του προσπιπτομένου ιστού. Το OCT μπορεί να απεικονίσει, με ανάλυση από 10 έως 20 μm, μικροδομές του αγγειακού τοιχώματος με εξαίσια λεπτομέρεια. Μέχρι σήμερα, η δυνατότητα εφαρμογής της μεθόδου είχε περιοριστεί σε μικρές αρτηρίες διαμέτρου έως 4mm και δεν είχε εφαρμοστεί in vivo στα αγγεία των κάτω άκρων, κάτωθεν του επιπέδου των βουβώνων. Σκοπός της παρούσας μελέτης είναι να αναφερθεί για παγκοσμίως πρώτη φορά η ασφάλεια και η σκοπιμότητα της απεικόνισης με Οπτική Συνεκτική Τομογραφία του αρτηριακού άξονα των κάτω άκρων , κάτωθεν του επιπέδου της βουβώνας ( μηροϊγνυακός άξονας και κνημιαία αγγεία), καθώς και οι σχετιζόμενες με το FD-OCT επιπλοκές. Επιπρόσθετα, να διερευνηθούν για πρώτη φορά, με τη χρήση FD-OCT, τα χαρακτηριστικά του αγγειακού τοιχώματος του ανωτέρω άξονα (τόσο πριν όσο και μετά από αγγειοπλαστική ή/και τοποθέτηση stent), η μορφολογία της αθηρωματικής πλάκας, η μορφολογία και η ποσοτικοποίηση της υπερπλασίας του νέου εσωτερικού χιτώνα (neointima) εντός του stent, η επαναστένωση εντός του stent (ISR) και η κακή εναπόθεση (malapposition) των stent struts σε μια σειρά από ασθενείς που πάσχουν από περιφερική αρτηριοπάθεια (PAD). Μελετήθηκαν, με ποσοτική ανάλυση του αυλού τους (Quantitative vascular analysis), αρτηρίες με διάμετρο έως 7 χιλιοστά. Μικτά χαρακτηριστικά από περιοχές πλούσιες σε λιπίδια, εναποθέσεις ασβεστίου και ασβεστοποιημένες πλάκες, νεκρωτικές περιοχές και ίνωση εντοπίστηκαν σε όλες τις απεικονιζόμενες αθηροσκληρωτικές βλάβες. Ωστόσο, με βάση το επικρατέστερο από τα παραπάνω απεικονιστικά χαρακτηριστικά, οι βλάβες στο πλαίσιο της έρευνας ταξινομήθηκαν ως αμιγώς ινωτικές, ως ινοασβεστοποιημένες, ως πλούσιες σε λιπίδια και τέλος ως νεκρωτικές/ασβεστοποιημένες. Συσσώρευση των μακροφάγων εντός της αθηρωματικής πλάκας σημειώθηκε σε μικρό ποσοστό των de novo αθηρωματικών αλλοιώσεων. Ποικίλοι βαθμοί υπερπλασίας του νέου έσω χιτώνα απεικονίσθηκαν σε όλες τις περιπτώσεις ISR αλλοιώσεων, με καθαρά ινωτικά χαρακτηριστικά και σημαντική νεοαγγείωση σε κάποιες από αυτές. Η νεοαγγείωση συνέπεσε με το επίπεδο της μέγιστης στένωσης του αγγειακού αυλού. Σημαντικού βαθμού διαχωρισμός με μεγάλο περιορισμό του αγγειακού αυλού, τέτοιος ώστε να απαιτηθεί να τοποθετηθεί ενδοαυλικό stent, ανιχνεύθηκε σε αρκετές περιπτώσεις της de novo αθηρωμάτωσης. Η ψηφιακή αφαιρετική αγγειογραφία παρέλειψε να προσδιορίσει μεγάλο ποσοστό των σοβαρών διαχωρισμών μετά από αγγειοπλαστική. Η νεοαθηροσκλήρυνση εντός του νέου έσω χιτώνα των κνημιαίων φαρμακευτικών stents (DES), είναι ένα συχνό εύρημα τόσο στους συμπτωματικούς όσο και στους ασυμπτωματικούς ασθενείς. Μπορούμε να υποθέσουμε ότι, κατά αναλογία με τα εμφυτευμένα DES στα στεφανιαία αγγεία, η ελαττωματική ενδοθηλιοποίηση που προκαλείται από την εκλυόμενη φαρμακευτική ουσία, μαζί με την νεοαγγείωση που αναπτύσσεται μεταξύ των stent struts, μπορούν να υποδαυλίσουν την νεοαθηροσκλήρυνση εντός του νέου έσω χιτώνα των κνημιαίων DES, η οποία μπορεί να οδηγήσει σε επαναστένωση εντός του stent (ISR) και απώλεια του εμβαδού του αυλού των περιφερικών αρτηριών. Οι παρατηρήσεις της μελέτης αυτής θέτουν σε αμφισβήτηση το παραδοσιακό τρόπο κατανόησης της περιφερειακής επαναστένωσης εντός του stent ως μιας απλής υπερπολλαπλασιαστικής απάντησης στο βαρότραυμα. Η απεικόνιση με FD-OCT είναι ένα βέλτιστο πειραματικό εργαλείο για την αξιολόγηση της εξέλιξης της αθηροσκληρωματικής νόσου και την επαναστένωση του αγγείου. Μπορεί να παρέχει υψηλής ευκρίνειας ενδοαγγειακή απεικόνιση κατά τη διάρκεια αγγειοπλαστικών επεμβάσεων στα κάτω άκρα και θα μπορούσε να αποδειχθεί κλινικά χρήσιμο για τον προσδιορισμό της εντός του stent πρόπτωσης ιστού και του strut malapposition. Παρ 'όλα αυτά, δεν πρέπει να χρησιμοποιηθεί ως εργαλείο για τη συνήθη κλινική πρακτική μέχρι να προκύψουν στοιχεία από περαιτέρω κλινικές δοκιμές για τον καθορισμό των ειδικών ενδείξεων της απεικόνισης με FD-OCT στις περιφερικές αρτηρίες. / Optical coherence tomography (OCT) is a catheter-based imaging method that employs near-infrared light to produce high-resolution intravascular images. OCT can readily visualize vessel microstructure at a 10- to 20-μm resolution with exquisite detail. To date, however, applicability of the method has been limited to small diameter arteries (≤4 mm). To the best of the author’s knowledge, this study is the first worldwide that demonstrates the safety and clinical feasibility of frequency domain Optical Coherence Tomography (FD-OCT) imaging of infrainguinal vessels in vivo during infrainguinal angioplasty procedures. It is also the first study that reports the use of intravascular FD-OCT to detect and characterize in-stent neointimal tissue following infrapopliteal drug eluting stent (DES) placement in patients suffering from critical limb ischemia. Quantitative lumen analysis of arteries with diameter up to 7 mm was performed. High-resolution OCT images provided exquisite two-dimensional axial and longitudinal views of the infrainguinal arteries and allowed thorough investigation of a variety of angioplasty sequela, including and not limited to intimal tears and dissection flaps, white and red thrombus, stent mesh malapposition, and intrastent plaque prolapse. Of interest, OCT identified cases of suboptimal postangioplasty outcome that single-plane subtraction angiography did not recognize and accounted. Mixed features of lipid pool areas, calcium deposits and calcified plaques, necrotic areas, and fibrosis were identified in all of the imaged atherosclerotic lesions. However, based on the predominant baseline imaging findings, lesions under investigation were classified as purely fibrotic, fibrocalcific, mostly lipid-laden and necrotic/calcified. Intraplaque accumulation of macrophages was noted in some of de novo atheromatic lesions. Varying degrees of neointimal hyperplasia were demonstrated in all cases of in stent restenosis (ISR) lesions with purely fibrotic features and considerable neovascularization in some of them. The latter finding coincided with the level of maximum vessel stenosis in all cases. Neoatherosclerosis following infrapopliteal DES placement is a frequent finding in both symptomatic and asymptomatic patients. Our preliminary observations allow us to speculate that analogous to coronary implanted DES, defective endothelialization induced by the eluted drug, along with neovascularization developing between the stent struts, may incite neointimal neoatherosclerosis, which may result in ISR and lumen loss of the peripheral arteries. It also seems that infrapopliteal neoatherosclerosis may be a significant contributing factor for ISR rather than a minor and sporadic process, highlighting the clinical significance of the phenomenon. Our observations put in dispute the traditional way of understanding peripheral in-stent restenosis as a simple hyperproliferative response to barotraumas and may explain the paramount importance of aggressive risk factor modification strategies. Neointimal neoatherosclerosis as identified by FD-OCT may have a role in the development of below-the-knee restenosis and thus warrants further investigation by larger controlled studies. Moreover, it may prove clinically useful for the determination of intrastent tissue prolapse and strut malapposition. FD-OCT should not be utilized as a tool for routine clinical practice until evidence from further clinical trials emerge to determine the specific indications for OCT imaging of the peripheral arteries.