Author(s)

Shérrira M. Garavelo¹, Jaqueline J. Pereira¹, Nilsa S. Y. Wadt¹, Marcia M. Reis¹, Renata N. Ikegami¹, Joyce T. Kawakami¹, Abdelali Agouni^2,3, Suely A. P. Palomino¹, Dulcinéia Abdalla⁴, Maria de Lourdes Higuchi¹

¹Heart Institute (InCor), University of Sao Paulo Clinics Hospital, Sao Paulo, Brazil.
²Faculty of Health and Medical Sciences (FHMS), University of Surrey, Guildford, UK.
³College of Pharmacy, Qatar University, Doha, Qatar.
⁴Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

Background: Previous studies showed that atherosclerotic plaque vulnerability was related with microparticles (MPs)-vesicles larger than 100 nm, which released MMP9 collagenase. In our previous study, intramuscular injection of a new drug (PTCTS) normalized oxidized LDL serum levels and reduced rabbit atherosclerosis. Now, we studied administration of oral PTCTS in order to clarify anti-atherosclerotic mechanism of action, analyzing if the treatment removed MPs containing ox-LDL and Mycoplasma pneumoniae antigens and improved the immune response. Methods: We compared two groups of rabbits. Control group (CG, n = 6)—1% cholesterol enriched diet for 12 weeks; Treated group (TG, n = 8)—1% cholesterol enriched diet for 12 weeks with administration of PTCTS (400 μl/day) during the last 6 weeks of diet. The animals had their blood collected, in three different phases of the protocol before being fed with hypercholesterolemic diet, before being treated with water or PTCTS and at the moment of sacrifice. The serum was submitted to immunofluorescence technique to evaluate the quantity of microparticles marked with antibodies against Mycoplasma pneumoniae and ox-LDL. A fragment of aorta was submitted to immunohistochemical detection of antigens from MMP9, ox-LDL, NF-κB and IL-1β. Results: PTCTS showed significant reduction in MMP-9 (P = 0.001) and a tendency of reducing IL-1β (P = 0.09) in the aortic plaques compared with CG. In the serum, PTCTS was able to remove microparticles containing antigen of ox-LDL (P = 0.004) and Mycoplasma pneumoniae (P < 0.001). Conclusion: Oral treatment with PTCTS presented more adequate inflammatory response by reducing levels of ox-LDL, IL-1β and mycoplasma, as well as a better stabilization of the atheromatous plaque by reducing levels of MMP-9, avoiding plaque rupture, without causing mortality or toxicity.

Atherosclerosis, Inflammation, PTCTS, Mycoplasma, NF-κB

Garavelo, S. , Pereira, J. , Wadt, N. , Reis, M. , Ikegami, R. , Kawakami, J. , Agouni, A. , Palomino, S. , Abdalla, D. and Higuchi, M. (2015) Oral PTCTS (Particulated Transialidase) Removes Serum Microparticles and Decreases Inflammation in Atherosclerotic Plaques of Rabbits. Advances in Nanoparticles, 4, 107-115. doi: 10.4236/anp.2015.44012.