A B Cell Depleting Agent for the Treatment of Atherosclerosis
a technology of atherosclerosis and b cell depletion, which is applied in the direction of antibody medical ingredients, drug compositions, peptides, etc., can solve the problems of plaque vulnerability, development of atherosclerotic lesions, and the depletion of b cells is not a promising treatment method
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B Cell Depletion and Atherosclerosis
[0098]Results and Discussion
[0099]The development of atherosclerosis is associated with signs of B cell activation, particularly manifested by enhanced production of natural IgM type and adaptive IgG types anti-oxidized low-density lipoprotein (ox-LDL) (auto)antibodies (Caligiuri et al., 2002; Shaw et al., 2000). However, in contrast to other immune-mediated diseases, i.e., rheumatoid arthritis and systemic lupus erythematosus, B cells have been assigned a protective role in atherosclerosis (Caligiuri et al., 2002; Major et al., 2002; Binder et al., 2004; Miller et al., 2008). Although IgG types anti-ox-LDL antibodies show variable association with vascular risk, circulating levels of IgM type anti-ox-LDL antibodies have been more frequently linked with reduced vascular risk in humans (Karvonen et al., 2003; Tsimikas et al., 2007). In mice, IL-5- and IL-33-mediated atheroprotective effects have been indirectly associated with specific B1 cell acti...
example 2
B Cell Depletion is Associated with an Increase In Fractional Shortening in a Myocardial Infarction Model
[0118]Myocardial infarction was induced in 8 weeks old male C57BL6J mice by ligation of the left anterior descending coronary artery. One hour after myocardial ischemic injury mice were treated or not by intraperitoneal injection of a mouse monoclonal CD20 antibody (160 μg). Inventors showed that B cells infiltrated the infarct area. Blood B cells levels were analyzed by flow cytometry at days 1, 3, 7 and 14 after MI. The percentage of IgM+ B220+-B cells was markedly reduced after CD20 antibody treatment. Mice were sacrificed at day 14 post-MI and cardiac function was measured by echocardiography (FIG. 14). Such treatment was associated with an increase in fractional shortening suggesting that said treatment may be beneficial for the treatment of myocardial infarction.
example 3
Effects of B Cell Depletion in Abdominal Aortic Aneurysm
[0119]First, inventors use a validated mouse model of aneurysm formation. Apoe− / − mice fed a chow or high fat diet develop abdominal aortic aneurysm when infused with angiotensin (Ang) II for 28 days (Daugherty A et al, 2000). This model reproduces the accumulation of inflammatory cells, including B cells, within and around the aneurysmal vessel.
[0120]For more precise results, inventors may also use a new model of aortic aneurysm with a high incidence of aneurysm rupture, described in patent application WO2009056419. The model uses Apoe+ / + or Apoe− / − mice, and associates both AngII infusion and neutralization of TGF-β activity, two factors with a high relevance to the human disease. In this model, systemic neutralization of TGF-β activity leads to unexpected and marked increase in the susceptibility of these mice to AngII-induced aortic aneurysm (92.5%), and to a high level of mortality from aortic dissection and rupture (65%)....
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