PCSK9-related LDL-C value is correlated to Rab5 isoform expression level Faezeh Naseri a , Asghar Mohammadi a , Bita Hosseni a , Mohammad Shabani a , Sadegh Piran a , Elham Soltanmohammadi b , Mohammad Najafi a,c, ⁎ a Iran University of Medical Sciences, Medical School, Biochemistry Department, Iran b Iran University of Medical Sciences, School of Medicine-International Branch, Iran c Iran University of Medical Sciences, Cellular and Molecular Research Center, Iran abstract article info Article history: Received 22 October 2016 Received in revised form 6 December 2016 Accepted 28 December 2016 Available online 4 January 2017 Circulating LDL metabolism is mostly related to the LDL internalization and intracellular lysosome-related degra- dation events. In this way, the competitive biologic agents and vesicular membrane-integrated or assembled pro- teins are important functioning factors. The aim of this study was to investigate the relationships between Rab5, Rab7, Lamp1 and Lamp2 gene expression levels, circulating PCSK9 value and, serum LDL-C level. One hundred ten subjects were recruited from healthy adults. Lipid profile was measured by laboratory routine techniques. PCSK9 value was measured with ELISA Kit. The Rab5, Rab7, Lamp1 and Lamp2 gene expression levels of buffy coat sam- ples were measured using Real-Time qPCR technique. Serum LDL-C level was correlated to Rab5 expression level (r 0.25, p 0.02) and circulating PCSK9 value (r 0.3, p 0.003). Although PCSK9 elevated positively with LDL-C value but the Rab5 expression level increased up to 75 centiles. Furthermore, multiple regression analyses showed that the Rab5 expression level is significantly correlated to LDL-C value (p 0.025, β 0.003), age (p 0.037, β -0.006) and Lamp1 expression (p 0.001, β 0.079) while the Rab7 expression level did not relate to the study factors ex- cept for Lamp1 (p 0.011, β 0.053). The results proposed that the LDL-C-correlated Rab5 expression level may be a primary cellular response due to reduced PCSK9-associated LDL influx. Furthermore, the LDL-C value was not cor- related to Lamp1 and Rab7 expression levels. Our data suggested that the vesicular structures may be reduced with age. © 2017 Elsevier Inc. All rights reserved. Keywords: Rab5 Rab7 Lamp1 Lamp2 PCSK9 LDL-C 1. Introduction Atherosclerosis is one of the main causes of morbidity and mortality in the world (Cahill and Redmond, 2016). It is improved due to endo- thelial progressive dysfunctions and, inflammatory events in the ves- sels. The recent studies have been updated traditional risk factors by incorporating molecular, immunological, genetic, imaging, and bio- physical agents since finding of critical risk factors play major roles in prevention of atherosclerosis (Vrablík, 2015). Lipidemia is one of main risk factors emerged in the atherosclerosis hypotheses (Bragg and Walling, 2015). Many studies reported that lipid abnormalities such as hypercholesterolemia, hypertriglyceridemia and HDL metabolism dis- orders are mostly related to prevalence of cardiovascular diseases (CVD). Furthermore, abnormal lipoproteins, such as Lp(a), are also re- ported to involve in cardiovascular diseases (Manocha and Srivastava, 2016). In usual, the lysosome degradation of LDL particles and their transportation occur by hydrolytic enzymes and membrane trans- porters. The lysosome proteins are mostly synthesized in the trans- Golgi network (TGN) and are sorted by mannose 6-phosphate receptors (MPRs). They are also involved in other cellular functions such as trans- portation, luminal resistance to enzyme degradation and, fusion with endosomes, phagosomes, and cytoplasmic membranes (Maxfield, 2014; Peters et al., 2016). Rab proteins are known as small molecular GTPases that switch con- formational changes through Rab-GDP/GTP modes. Although the roles of majority of Rab proteins are not known but they regulate widely ve- sicular transport via endocytosis and exocytosis processes. Many evi- dences reported that the Rab proteins are specifically involved in the control of vesicle docking and fusion (Jordens et al., 2005). Recent find- ings have been shown that activated Rab proteins can selectively bind to their effectors in order to recruit other lysosomal membrane proteins, to facilitate the subsequent transport through vesicular structures and to participate in docking and fusion processes (Wandinger-Ness and Zerial, 2014). These findings suggested that the Rab isoforms may be as central regulators in the vesicular transport processes. Furthermore, Rab5 is known as a maturing agent to improve the early endosome (Bean et al., 2015). It may be a scaffold for assembling at least twenty Gene Reports 6 (2017) 128–131 Abbreviations: CVD, cardiovascular diseases; TGN, trans-Golgi network; MPRs, man- nose 6-phosphate receptors; PCSK9, proprotein convertase subtilisin/kexin type 9; LDLR, LDL receptor; LAMP1, lysosomal associated membrane protein 1; LAMP2, lysosomal asso- ciated membrane protein 2; HRP, horseradish peroxidase. ⁎ Corresponding author at: Cellular and Molecular Research Center, Biochemistry Department, Iran University of Medical Sciences, Medical School, Tehran, Iran. E-mail address: nbsmmsbn@iums.ac.ir (M. Najafi). http://dx.doi.org/10.1016/j.genrep.2016.12.012 2452-0144/© 2017 Elsevier Inc. All rights reserved. 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