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Hollow/porous nanoparticles, including nanocarriers, nanoshells, and mesoporous materials have applications in catalysis, photonics, biosensing, and delivery of theranostic agents. Using a hierarchical template synthesis scheme, we have synthesized a nanocarrier mimicking a golf ball, consisting of (i) solid silica core with a pitted gold surface and (ii) a hollow/porous gold shell without silica. The template consisted of 100 nm polystyrene beads attached to a larger silica core. Selective gold plating of the core followed by removal of the polystyrene beads produced a golf ball-like nanostructure with 100 nm pits. Dissolution of the silica core produced a hollow/porous golf ball-like nanostructure.

Psoriasis is a systemic inflammatory disease with increased risk of atherosclerotic events and premature cardiovascular disease. S100A7, A8/A9, and A12 are protein complexes that are produced by activated neutrophils, monocytes, and keratinocytes in psoriasis. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature previously found to be associated with cardiovascular risk factors and psoriasis severity. LRNC can decrease with biologic therapy, but how this occurs remains unknown. We investigated the relationship between S100 proteins, LRNC, and biologic therapy in psoriasis. S100A8/A9 associated with LRNC in fully adjusted models (β = 0.27, P= 0.009, n=125 psoriasis patients with available coronary CT angiography scans, LRNC analyses, and serum S100A7, S100A8, S100A9, S100A12, and S100A8/A9 levels). At one year, in patients receiving biologic therapy (36 of 73 patients had 1-year CCTA scans available), a 79% reduction in S100A8/A9 levels (-172 (-291.7-26.4) vs -29.9 (-137.9- 50.5) P= 0.04) and a 0.6 mm2reduction in average LRNC area (0.04 (-0.48-0.77) vs -0.56 (-1.8- 0.13); P= 0.02) were noted. These results highlight the potential role of S100A8/A9 in the development of high-risk coronary plaque in psoriasis.

Introduction:Psoriasis (PSO) is a chronic inflammatory condition associated with elevated non-calcified coronary plaque, high-risk plaque features and increased risk of major cardiovascular events. We recently demonstrated beneficial effects of biologic therapies (anti-TNF, anti-interleukin12/23 and anti-interleukin17) on coronary plaque in PSO following one-year treatment. However, the components of lipid-rich necrotic core (LRNC) and positive remodeling in response to biologic therapy were not fully characterized.Methods:Consecutive biologic na?ve patients (n=92), stratified by biologic therapy, underwent coronary computed tomography angiography (320 detector row, Toshiba) at baseline and 1-year. We studied maximal lipid-rich necrotic core area and maximal remodeling ratio for each major coronary vessel using a novel software (vascuCAP Elucid Bioimaging, Wenham, MA), which has been validated with vascular human histopathology.Results:Study participants were middle-aged (?=51), predominantly male with low cardiovascular risk by Framingham risk score, and moderate-severe PSO in both groups. Positive remodeling but not LRNC was associated with PSO severity (?=0.16, p=0.009; ?=0.05, p=0.44). Patients started on a biologic therapy at baseline experienced a significant decrease in LRNC (3.3?2.6?m2vs 2.9?2.1?m2; p=0.038) and positive remodeling (defined as >1.4) (n%: 11% vs 6%; p=0.03) at 1-year follow-up. In contrast, participants receiving no biologic treatment over 1-year tended towards larger LRNC (2.8?1.9?m2vs 2.9?1.7?m2; p=0.11) and had no change in positive remodeling (11% vs 11%; p=1.00).Conclusions:At 1-year follow-up, biologic treatment was associated with favorable modification of lipid-rich necrotic core and positive remodeling, whereas non-biologic treatment tended to worsen these features. These findings add to the body of literature that anti-inflammatory therapy may affect CV risk in psoriasis.

Introduction:Psoriasis, a chronic inflammatory skin disease, is associated with HDL dysfunction assessed as cholesterol efflux capacity (CEC), and increased high-risk coronary plaque (HRP) by coronary computed tomography angiography (CCTA). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a scavenger receptor for oxidized low-density lipoprotein, is critical to the development of HDL dysfunction, and lipid-rich high-risk atherosclerotic plaques. We aimed to understand the relationships of soluble LOX-1 (sLOX-1) with CEC, and HRP in psoriasis.Methods:Consecutive psoriasis patients (n=175) underwent CCTA scans and ELISA to identify HRP (Medis, Netherlands) and measure sLOX-1 (Medimmune, USA) respectively. HRP was characterized as a low attenuation plaque or a positively remodeled plaque or both. CEC was measured in duplicate using a validated cell-based ex vivo assay.Results:Psoriasis patients were middle-aged, predominantly male, with low CV risk by Framingham risk and had moderate-severe psoriasis severity (Table 1). sLOX-1 negatively associated with CEC in unadjusted (?=-0.17, p=0.03) as well as when adjusted for Framingham risk score, body mass index, hs-CRP, statin use, and biologic psoriasis treatment (?=-0.19, p=0.02). Moreover, patients with higher sLOX-1 (dichotomized based on mean sLOX-1 levels in psoriasis) were at significantly higher odds of prevalent high-risk plaque in adjusted analyses [odds ratio (OR): 3.47; 95% confidence interval (CI): 1.110-10.819, p=0.03] with positive remodeling in the coronary artery, associating with circulating sLOX-1 in fully adjusted models (?=0.10, p=0.04).Conclusions:sLOX-1 was significantly associated with CEC and HRP in psoriasis, demonstrating the potential role of sLOX-1 in HDL dysfunction and subclinical cardiovascular disease in psoriasis. Our findings support further studies evaluating sLOX-1 in chronic inflammation associated cardiometabolic disease.

Introduction:Breast arterial calcification (BAC), detectable on mammography, has emerged as a potential risk stratification tool and surrogate marker of cardiovascular disease that comes with no additional cost or radiation. The association between BAC and heart failure (HF) is unclear.Methods:This single-center, retrospective study included 278 women from 2006-2016 who had both digital mammography and coronary computed tomography (CT) within one year of each other. BAC was quantified using an automated algorithm and compared with the presence of HF. Prevalent or incident HF was determined based upon review of medical records through September 2018.Results:Among the 278 women, mean age was 61?11 years; 22% had diabetes, 54% had hypertension, 53% had hyperlipidemia and 29% were current or former smokers. BAC was detectable in 90 women (32%) and HF was present in 19 women (7%). Of the patients with HF, 68% had preserved left ejection fraction (mean 57%) and 84% were non-ischemic. On univariable analysis, higher BAC was associated with the presence or development of HF (odds ratio (OR) per standard deviation increase in lgBAC 2.30 [95% CI 1.30-4.09], p = 0.004). Even after adjusting for age, hypertension and diabetes, the association was maintained (OR 2.20 [95% CI 1.17-4.15], p = 0.01).Conclusions:BAC was independently associated with the presence or development of HF. BAC may represent an early marker of vascular stiffness and endothelial dysfunction and may be useful for identifying women at increased risk of HF. Additional studies are needed to validate and elucidate this association.