Oral PTCTS (Particulated Transialidase) Removes Serum Microparticles and Decreases Inflammation in Atherosclerotic Plaques of Rabbits

Abstract

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 sig-S. M. Garavelo et al. 108 nificant 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.

Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response

“…The hypoxia that occurs during MI increases the production of mitochondrial ROS, resulting in lipid peroxidation, which is a strong inflammatory signal that activates NF-κB. TNF-α and IL-1, cytokines that act as transcriptional activators in vascular endothelial cells, also participate in the activation of the NF-κB pathway by regulating many of its regulatory genes and amplifying the immune response 25 . However, anti-inflammatory mediators such as IL-10 and IL-13 suppress production of TNF-α and IL-1, in turn suppressing NF-κB activation by preventing the inactivation of I-κBα.…”

Commentary: Comparison of the Protective Effects of Individual Components of Particulated trans-Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits

“…The Nutricosmetic with PTCTS, combining transialidase enzyme with nanoparticles derived from orchid extracts, was able to remove archaea. This nutricosmetic agent in experimental work with atherosclerotic rabbits lead to reduction of inflammation in plaques in parallel with removal of microvesicles from serum arteries, without side effects (4, 21).…”

Interação do micoplasma e do SUMO na aterogênese e na resposta antilipemiante e anti-inflamatória do composto PTCTS em coelhos com dieta hipercolesterolêmica

“…Micoplasmas são bactérias da classe Mollicutes, com poucas organelas e que crescem em simbiose, interagindo com células do hospedeiro 6 , porque não conseguem sintetizar muitas moléculas essenciais, como os aminoácidos, ácidos graxos e colesterol precisando buscá-los no ambiente do hospedeiro.…”