No abstract

Figure 10Effect of lipid competitors on the binding of NO 2 -LDL to CD36-transfected cells. [ 125 I]LDL was modified as described for the complete system in Figure 2a. [ 125 I]-NO 2 LDL (5 µg/mL) was then incubated with CD36-expressing 293 cells for 3 hours at 4°C in the presence of (a) 20 µg lipid/mL or (b) the indicated concentrations (µg lipid/mL) of competitors. PAPC, PAPC(SnCl 2 ), PLPC, and POPC unilamellar vesicles were oxidized for 8 hours at 37°C as described for the complete system in Figure 2 in the presence (+NO 2 -, filled symbols) or absence (-NO 2 -, open symbols) of NO 2 -. Where indicated, BSA (0.2 mg protein/mL final concentration) was also included during liposome preparation as described in Methods (hatched bars). PAPC (SnCl 2 ), hydroperoxide-free PAPC generated by reduction of PAPC with SnCl 2 , and then reisolation of PAPC under argon atmosphere before use, were used as described in Methods. Data represent the mean ± SD of triplicate determinations (a) or means of triplicate determinations (b) of a representative experiment performed 3 times. A P < 0.001 for comparison versus control (no competitor).

Cardio-oncology has organically developed as a new discipline within cardiovascular medicine as a result of the cardiac and vascular adverse sequelae of the major advances in cancer treatment. Patients with cancer and cancer survivors are at increased risk of vascular disease for a number of reasons. First, many new cancer therapies, including several targeted therapies, are associated with vascular and metabolic complications. Second, cancer itself serves as a risk factor for vascular disease, especially by increasing the risk for thromboembolic events. Finally, recent data suggest that common modifiable and genetic risk factors predispose to both malignancies and cardiovascular disease. Vascular complications in patients with cancer represent a new challenge for the clinician and a new frontier for research and investigation. Indeed, vascular sequelae of novel targeted therapies may provide insights into vascular signaling in humans. Clinically, emerging challenges are best addressed by a multidisciplinary approach in which cardiovascular medicine specialists and vascular biologists work closely with oncologists in the care of patients with cancer and cancer survivors. This novel approach realizes the goal of providing superior care through the creation of cardio-oncology consultative services and the training of a new generation of cardiovascular specialists with a broad understanding of cancer treatments.

We have analyzed the amino acid sequences situated around the putative proteolytic cleavage sites in twenty different biosynthetic precursors of peptide hormones by processing enzymes. The prediction of the probability for forming secondary structures around the basic amino acids, constituting the cleavage sites, was made using the modified method of Chou and Fasman. The results indicate that the processing sequences which are cleaved in vivo, are in ail cases located inside regions with high B-turn formation probability or else immediately adjacent to these structures. The p-turn forming region at the cleavage locus, is flanked on both sides by amino acid sequences with a high probability for forming highly ordered structures, either /?-sheet or cc-helix. These conformational features are not found in precursors around dibasic pairs, i.e. putative cleavage loci, but which are not cleaved in vivo and appear to be conserved. We hypothesize that p-turns including the basic amino acids doublets, flanked by highly ordered secondary structures (either b-sheet or a-helix) may constitute a minimal requirement for the recognition by the endoproteases involved in the processing of these precursors. Proteolytic processing