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Although the use of aortoiliac endarterectomy to treat occlusive disease has declined since the advent of endovascular procedures and operative bypass grafting techniques, clinical scenarios still exist in which it can be useful. We present the case of a patient with right lower extremity pain at rest, an anomalous right pelvic kidney, right common iliac artery occlusion, and severe left common iliac artery stenosis. We have demonstrated that aortoiliac endarterectomy should not be considered an outdated surgical technique but a viable alternative for revascularization in a specific subset of patients.

Background Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which differential methylation in saliva at baseline was associated with maternal obesity status. The current study investigated to what extent baseline DNA methylation in salivary samples in these 3–5-year-old Hispanic children predicted the incidence of childhood obesity in a 3-year prospective cohort. Methods We examined a subsample (n = 92) of Growing Right Onto Wellness (GROW) trial participants who were randomly selected at baseline, prior to randomization, based on maternal phenotype (obese or non-obese). Baseline saliva samples were collected using the Oragene DNA saliva kit. Objective data were collected on child height and weight at baseline and 36 months later. Methylation arrays were processed using standard protocol. Associations between child obesity at 36 months and baseline salivary methylation at the previously identified 17 CpG dinucleotides were evaluated using multivariable logistic regression models. Results Among the n = 75 children eligible for analysis, baseline methylation of Cg1307483 (NRF1) was significantly associated with emerging childhood obesity at 36-month follow-up (OR = 2.98, p = 0.04), after adjusting for child age, gender, child baseline BMI-Z, and adult baseline BMI. This translates to a model-estimated 48% chance of child obesity at 36-month follow-up for a child at the 75th percentile of NRF1 baseline methylation versus only a 30% chance of obesity for a similar child at the 25th percentile. Consistent with other studies, a higher baseline child BMI-Z during the preschool period was associated with the emergence of obesity 3 years later, but baseline methylation of NRF1 was associated with later obesity even after adjusting for child baseline BMI-Z. Conclusions Saliva offers a non-invasive means of DNA collection and epigenetic analysis. Our proof of principle study provides sound empirical evidence supporting DNA methylation in salivary tissue as a potential predictor of subsequent childhood obesity for Hispanic children. NFR1 could be a target for further exploration of obesity in this population.

OBJECTIVE. Previous studies have shown hydrogen sulfide (H(2)S) exerts potent proangiogenic properties under in vitro conditions and in rodent models. We sought to determine whether a novel H(2)S prodrug promotes peripheral revascularization in a swine model of acute limb ischemia (ALI). METHODS AND RESULTS. ALI was induced in 17 female miniswine via intravascular occlusion of the external iliac. At day 7 post- ALI induction, miniswine (n = 17) were randomized to received placebo or the H(2)S pro-drug, SG-1002 (800 mg PO BID), for 35 days. At day 35 SG-1002 increased circulating levels of H(2)S (5.0 ± 1.2 μmol/L vs. 1.8 ± 0.50 μmol/L; p < 0.05), sulfane sulfur (10.6 ± 2.3 μmol/L vs. 2.6 ± 0.8 μmol/L; p < 0.05), and nitrite (0.5 ± 0.05 μmol/L vs. 0.3 ± 0.03 μmol/L; p < 0.005) compared to placebo. SG-1002 therapy increased angiographic scoring in ischemic limb vessel number (27.6 ± 1.6 vs. 22.2 ± 1.8; p < 0.05) compared to placebo. Treatment with SG-1002 preserved existing capillaries in ischemic limbs (128.3 ± 18.7 vs. 79.0 ± 9.8 capillaries/mm(2); p < 0.05) compared to placebo. Interestingly, treatment with SG-1002 also improved coronary vasorelaxation responses to bradykinin and substance P in miniswine with ALI. CONCLUSIONS. Our results suggest that daily administration of the H(2)S prodrug, SG-1002, leads to an elevation in circulating H(2)S and NO signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease.

Background Zofenopril, a sulfhydrylated angiotensin‐converting enzyme inhibitor (ACEI), reduces mortality and morbidity in infarcted patients to a greater extent than do other ACEIs. Zofenopril is a unique ACE I that has been shown to increase hydrogen sulfide (H 2 S) bioavailability and nitric oxide ( NO ) levels via bradykinin‐dependent signaling. Both H 2 S and NO exert cytoprotective and antioxidant effects. We examined zofenopril effects on H 2 S and NO bioavailability and cardiac damage in murine and swine models of myocardial ischemia/reperfusion ( I /R) injury. Methods and Results Zofenopril (10 mg/kg PO ) was administered for 1, 8, and 24 hours to establish optimal dosing in mice. Myocardial and plasma H 2 S and NO levels were measured along with the levels of H 2 S and NO enzymes (cystathionine β‐synthase, cystathionine γ‐lyase, 3‐mercaptopyruvate sulfur transferase, and endothelial nitric oxide synthase). Mice received 8 hours of zofenopril or vehicle pretreatment followed by 45 minutes of ischemia and 24 hours of reperfusion. Pigs received placebo or zofenopril (30 mg/daily orally) 7 days before 75 minutes of ischemia and 48 hours of reperfusion. Zofenopril significantly augmented both plasma and myocardial H 2 S and NO levels in mice and plasma H 2 S (sulfane sulfur) in pigs. Cystathionine β‐synthase, cystathionine γ‐lyase, 3‐mercaptopyruvate sulfur transferase, and total endothelial nitric oxide synthase levels were unaltered, while phospho‐endothelial nitric oxide synthase 1177 was significantly increased in mice. Pretreatment with zofenopril significantly reduced myocardial infarct size and cardiac troponin I levels after I /R injury in both mice and swine. Zofenopril also significantly preserved ischemic zone endocardial blood flow at reperfusion in pigs after I/R. Conclusions Zofenopril‐mediated cardioprotection during I /R is associated with an increase in H 2 S and NO signaling.

Background: Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing heart. These maladaptive structural changes can worsen cardiac function accelerating the progression to decompensated heart failure (HF). We investigated the effects of a novel inhibitor of the conversion of normal fibroblast to the myofibroblast phenotype in the setting of pressure overload induced HF. Methods: Male C57BL/6J mice (10 wks) were subjected to transverse aortic constriction (TAC; 27 g needle) and NM922 (NovoMedix, LLC50 mg/kg/d i.p.) or VEH (DMSO + HS-15) was administered daily starting at 6 wks post TAC. Echocardiography was assessed at baseline and for 16 wks post TAC. At the 16 wk endpoint, mice were sacrificed and hearts were collected for biochemical and molecular assessment. Results: NM922 significantly attenuated TAC-induced left ventricular (LV) dilation at 16 wks post TAC (LVEDD: 3.5 ± 0.1 vs. 4.5 ± 0.2 mm, p < 0.01; LVESD: 2.5 ± 0.2 vs. 3.8 ± 0.3 mm, p < 0.01) compared to VEH. NM922 treated mice displayed reduced wall thickening (LVPWd: 1.0 ± 0.03 vs. 1.2 ± 0.05 mm; p < 0.05) at 10 wks post TAC compared to VEH. LV ejection fraction (LVEF) was preserved in NM922 treated mice at 8-16 wks post TAC compared to VEH (*p < 0.05; **p < 0.001) compared to VEH. Treatment with NM922 resulted in reductions in heart (8.5 ± 0.5 vs. 12.0 ± 0.9 mg/mm; p < 0.01) and lung (8.2 ± 0.3 vs. 11.5 ± 0.6 mg/mm; p < 0.0001) weights compared to VEH. Picrosirius Red staining revealed that NM922 reduced cardiac interstitial collagen volume fraction by 50% (p < 0.05 vs. VEH). Circulating BNP levels trended toward lower (p = 0.08) in the NM922 mice when compared to VEH. Conclusion: Chronic treatment with NM922 following the onset of cardiac hypertrophy and HF resulted in attenuated myocardial collagen formation and adverse remodeling with preservation of LVEF. Future studies are aimed at further elucidation of the molecular and cellular mechanisms by which this novel agent protects the failing heart.