BiU RLChttp §^orelp(i^^130>Gine2 5 go Fha^0 l1t3K 7 a tabase of 200 subscribed and open-access titles in the biological^ ecological', ana environmental ' sciences published by nonprofit societies, associations, museums, institutions, and presses.

There are currently no serum-based evaluations that can corroborate the severity of peripheral artery disease (PAD). In this cross-sectional study, we assessed the prevalence of elevated serum fatty acid synthase (cFAS) in patients with chronic limb-threatening ischemia (CLTI) and evaluated the accuracy of its use in detecting this condition. Preoperative fasting serum samples from 87 patients undergoing vascular intervention were collected between October 2014 and September 2016. Median age was 62 years, with 56 (64%) men, and 32 (37%) with CLTI. We found that elevated cFAS content (OR 1.17; 95% CI 1.04–1.31), type 2 diabetes (T2D; OR 5.22; 95% CI 1.77–15.4), and smoking (OR 3.53; 95% CI 1.19–10.5) were independently associated with CLTI and could detect the presence of CLTI with 83% accuracy (95% CI 0.74–0.92). Furthermore, serum FAS content was positively correlated with FAS content in femoral artery plaque in patients with severe PAD ($${R}^{2}$$ R 2 = 0.22; P =  0.023). Finally, significantly higher co-localization of FAS and ApoB were observed within lower extremity arterial media (P < .001). Our findings indicate that serum FAS content is a marker for disease severity in patients with PAD, independent of concomitant T2D and smoking, and may play a key role in FAS and ApoB peripheral plaque progression.

ObjectivePeripheral atherosclerosis that accumulates in the extracranial carotid and lower extremity arteries can lead to significant morbidity and mortality. However, atherosclerotic disease progression is often not homogenous and is accelerated by diabetes. We previously observed increased phospholipid content in minimally (Min)-diseased arterial segments compared to maximally (Max)-diseased segments. Since Peroxisome Proliferator-Activated Receptor alpha (PPARα) is a key regulator of lipid metabolism, we hypothesized that it may have differential expression and signaling in Min vs. Max-diseased peripheral arterial segments.MethodsEighteen patients who underwent carotid endarterectomy (CEA), and 34 patients who underwent major lower extremity amputation were prospectively enrolled into a vascular tissue biobank. Min and Max-diseased segments were obtained in real-time from CEA plaque and amputated lower extremity arterial segments. mRNA and protein were isolated from specimens and the relative expression of ppara, and its downstream genes Acyl-CoA Oxidase 1 (acox1) and Carnitine Palmitoyltransferase 1A (cpt1a) were also evaluated. We evaluated gene expression and protein content relative to atherosclerotic disease severity and clinical diabetes status. Gene expression was also evaluated relative to Hemoglobin A1c and serum lipid profiles.ResultsIn CEA segments of patients with diabetes, we observed significantly higher ppara and acox1 gene expression (p &lt; 0.01 and p &lt; 0.001 respectively), and higher PPARα protein content (p &lt; 0.05). Hemoglobin A1c significantly correlated with expression of ppara (R2 = 0.66, p &lt; 0.001), acox1 (R2 = 0.31, p &lt; 0.05), and cpt1a (R2 = 0.4, p &lt; 0.05). There was no significant difference in gene expression between Min vs. Max-diseased CEA plaque segments. Conversely, in lower extremity arterial segments of patients with diabetes, we observed significantly lower ppara, acox1, and cpt1a expression (p &lt; 0.05, p &lt; 0.001, and p &lt; 0.0001 respectively). Interestingly, CPT1A content was lower in arterial segments of patients with diabetes (p &lt; 0.05). Hemoglobin A1c and HDL-cholesterol had negative correlations with ppara (R2 = 0.44, p &lt; 0.05; R2 = 0.42, p &lt; 0.05; respectively).ConclusionThis study demonstrates the significant differential expression of ppara and its immediate downstream genes in human carotid and lower extremity arteries relative to disease severity and diabetes. These findings highlight that mechanisms that influence atheroprogression in the carotid and lower extremities peripheral arteries are not homogenous and can be impacted by patient diabetes status and serum cholesterol profiles. Further elucidating these differential molecular mechanisms can help improve targeted therapy of atherosclerosis in different peripheral arterial beds.

Peripheral atherosclerosis manifests in both the extracranial carotid and lower extremity arteries and can lead to significant morbidity and mortality. However, atherosclerotic disease progression is often not homogenous and is accelerated by diabetes. We previously observed altered phospholipodomic profiles between minimally (MIN) and maximally (MAX) diseased peripheral arterial segments. Since Peroxisome Proliferator-Activated Receptor alpha ( pparα ) is a key regulator of lipid metabolism, we hypothesized that it may have variable content and signaling in MIN and MAX diseased arterial segments. To test our hypothesis, 12 patients who underwent carotid endarterectomy (CEA), and 19 patients who underwent major lower extremity amputation were recruited. MIN and MAX disease segments were obtained in real time from the operating room from CEA plaque and arterial segments from amputated lower extremities. mRNA was isolated from all specimens and relative content of pparα , Acyl-CoA Oxidase 1 ( acox1 ) , and Carnitine Palmitoyltransferase 1A ( cpt1a ) were evaluated. We observed significantly higher pparα expression in CEA segments in patients with diabetes (p < 0.01), as well as higher acox1 (p < 0.001) and cpt1a (p < 0.05) expression (A-C). Hemoglobin A1C had a significant correlation with ppara gene expression. There was no significant difference in gene expression between MAX and MIN diseased CEA plaque segments. Interestingly, we observed that in lower extremity arterial segments there was no difference in ppara , acox1 , and cpt1a in patients with and without diabetes, but downstream genes were significantly increased in MAX diseased arterial segments (D-F). This study demonstrates the variable expression pattern of pparα and its downstream genes in human peripheral arteries. Our findings suggest variable gene expression in different peripheral arterial beds, which may have an impact on mechanisms of disease progression and pharmacologic targeting.

within 30 days. The reduction in revision seen at 6 months and 1 year is likely driven by patient mortality, as well as progression to amputation. In addition, this study identifies patient characteristics that contribute to mortality, amputation, and revision.