Description: Crusts composed of nontronite and ferromanganese oxides were recovered from Explorer Ridge, a spreading ridge segment in the northeastern Pacific Ocean located off the west coast of Canada. The chemical and mineralogical composition of the crusts closely resembles that of the mound-like hydrothermal deposits recently discovered at the FAMOUS site on the Mid-Atlantic Ridge and on the Galapagos spreading centre. Compositional anomalies suggest that the crusts are precipitates of hydrothermal vent solutions which were ejected discontinuously and subsequently mixed with seawater.

Description: Concretions of iron and manganese oxides and hydrous oxidesóobjects commonly called manganese nodulesóare widely distributed not only on the deep-sea floor but also in shallow marine environments1. Such concretions were not known to occur north of Cape Mendocino in the shallow water zones bordering the North-East Pacific Ocean until the summer of 1966 when they were recovered by one of us (J. W. M.) in dredge samples from Jervis Inlet, a fjord approximately 50 miles north-west of Vancouver, British Columbia.

Description: Objective— Atherosclerosis is an inflammatory disease with multiple underlying metabolic and physical risk factors. Bone morphogenic protein 4 (BMP4) expression is increased in endothelium in atherosclerosis-prone regions and is known to induce endothelial inflammation, endothelial dysfunction, and hypertension. BMP actions are mediated by 2 different types of BMP receptors (BMPRI and BMPRII). Here, we show a surprising finding that loss of BMPRII expression causes endothelial inflammation and atherosclerosis. Approach and Results— Using BMPRII siRNA and BMPRII +/– mice, we found that specific knockdown of BMPRII, but not other BMP receptors (Alk1, Alk2, Alk3, Alk6, ActRIIa, and ActRIIb), induced endothelial inflammation in a ligand-independent manner by mechanisms mediated by reactive oxygen species, nuclear factor-KappaB, and reduced nicotinamide adenine dinucleotide phosphate oxidases. Further, BMPRII +/– ApoE –/– mice developed accelerated atherosclerosis compared with BMPRII +/+ ApoE –/– mice. Interestingly, we found that multiple proatherogenic stimuli, such as hypercholesterolemia, disturbed flow, prohypertensive angiotensin II, and the proinflammatory cytokine (tumor necrosis factor-α), downregulated BMPRII expression in endothelium, whereas antiatherogenic stimuli, such as stable flow and statin treatment, upregulated its expression in vivo and in vitro. Moreover, BMPRII expression was significantly diminished in human coronary advanced atherosclerotic lesions. Also, we were able to rescue the endothelial inflammation induced by BMPRII knockdown by overexpressing the BMPRII wild type, but not by the BMPRII short form lacking the carboxyl-terminal tail region. Conclusions— These results suggest that BMPRII is a critical, anti-inflammatory, and antiatherogenic protein that is commonly targeted by multiple pro- and antiatherogenic factors. BMPRII may be used as a novel diagnostic and therapeutic target in atherosclerosis.

Description: Objective— Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results— We demonstrate that CD25 + ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr –/– rag1 –/– mice. To investigate the role of ILCs in atherosclerosis, ldlr –/– rag1 –/– mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or IL-2/anti-IL-2 complexes that expand CD25 + ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti–IL-2-treated mice. These IL-2-treated mice had reduced very low–density lipoprotein cholesterol and increased triglycerides compared with controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila, and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2 complex–induced eosinophilia but did not change lesion size. Conclusions— This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in very low–density lipoprotein cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis.

Description: Objective— T cell immunoglobulin and mucin domain (Tim) proteins are expressed by numerous immune cells, recognize phosphatidylserine on apoptotic cells, and function as costimulators or coinhibitors. Tim-1 is expressed by activated T cells but is also found on dendritic cells and B cells. Tim-4, present on macrophages and dendritic cells, plays a critical role in apoptotic cell clearance, regulates the number of phosphatidylserine-expressing activated T cells, and is genetically associated with low low-density lipoprotein and triglyceride levels. Because these functions of Tim-1 and Tim-4 could affect atherosclerosis, their modulation has potential therapeutic value in cardiovascular disease. Approach and Results— ldlr –/– mice were fed a high-fat diet for 4 weeks while being treated with control (rat immunoglobulin G1) or anti-Tim-1 (3D10) or -Tim-4 (21H12) monoclonal antibodies that block phosphatidylserine recognition and phagocytosis. Both anti-Tim-1 and anti-Tim-4 treatments enhanced atherosclerosis by 45% compared with controls by impairment of efferocytosis and increasing aortic CD4 + T cells. Consistently, anti-Tim-4-treated mice showed increased percentages of activated T cells and late apoptotic cells in the circulation. Moreover, in vitro blockade of Tim-4 inhibited efferocytosis of oxidized low-density lipoprotein–induced apoptotic macrophages. Although anti-Tim-4 treatment increased T helper cell (Th)1 and Th2 responses, anti-Tim-1 induced Th2 responses but dramatically reduced the percentage of regulatory T cells. Finally, combined blockade of Tim-1 and Tim-4 increased atherosclerotic lesion size by 59%. Conclusions— Blockade of Tim-4 aggravates atherosclerosis likely by prevention of phagocytosis of phosphatidylserine-expressing apoptotic cells and activated T cells by Tim-4-expressing cells, whereas Tim-1-associated effects on atherosclerosis are related to changes in Th1/Th2 balance and reduced circulating regulatory T cells.