Dyslipidemia,oxidative stress,in ammation and apoptosis are common features in atherosclerosis disease leading to

stroke. However there are numerous diagnostic tools indicating atherosclerotic lesions status such as imaging tools

and evaluation of circulating indexes such as atherogenic index of plasma (AIP). But these markers don’t de nitely

re ect vessel in ammation and apoptosis signaling pathways in early stages. We therefore considered which circulat-

ing risk factors have stronger association with apoptosis related proteins in the carotid tissues. Hence the associations

between the expression of in ammation or apoptosis related proteins content and antioxidant enzymes activity,

of Ox-LDL were measured by ELISA.Log (TG/HDL-C) as aatherogenic index of plasma (AIP) was calculated. Correla-

tions were assessed by use of the nonparametric Spearman correlation coef cient. After 8 weeks feeding with high

cholesterol diet, the mean of lipidic pro le including TC,LDL-C, TG, OxLDL and AIP, MDA were higher in HD vs. ND

group (P<0.05 in all) as well as the immunoreactivity of p- p38 and c-caspase 3 were elevated in HD vs. ND(P<0.05

Roshanak Bayatmakoo et al.

in both). Antagonistically, the expression of bcl2, the activity of SOD and GPx as well as the capacity of total anti-

oxidants were reduced in HD vs. ND(P<0.05 in all). The association (with the expression of p- p38 or c-caspase 3 )

were signi cant also positive for variables of OxLDL and MDA (strongest; r= 0.874) but negative for SOD, GPx and

TAC(P<0.05 in all). The association (with the expression of bcl2 )were signi cant also negativefor variables of OxLDL

expression of c-caspase 3, p- p38 or bcl2 (r=0.45; p=0.08, r=0.44; p=0.08, r=-0.38; p=0.14 respectively). Findings

disease (Yang et al., 2012) is accompanied by some

changes in plasmatic lipid pro le and redox status (Tie

et al., 2014). Generally, the hyperlipidemias are of inter-

est to the physician in the context of risk factors for

2010, Klafke et al., 2015).

ship between HDL-c concentration and in ammatory

and oxidative stress biomarkers, there is controversial

data in some population (Vavrova et al., 2015).

In addition, a large body of studies investigated the

associations between HDL-c concentration and status

of in ammation, endothelial activation and oxidative

stress biomarkers (Silva et al., 2011). Recently, Klafke et

cholesterol induced oxidative stress injures the vascular

endothelium, a key step in the pathogenesis ofathero-

sclerosis (Watt et al., 2016).

Circulating levels of OxLDL in blood are increased

generally following dislipidemia and particularly hyper-

cholesterolemia (Levitan et al., 2010). There are con ict-

ing data on whether The levels of circulating OxLDL

correspond to the severity of vascular damage. How-

ever accumulative evidence have shown the atherogenic

 ed LDL autoantibody titers) could be used to evaluate

the clinical setting of high-risk carotid atherosclerosis

both in screening and in follow-up studies (Chiesa et al.,

1998). Another study has been showed that enhanced

1996).

- superoxidedismutase (EC-SOD) (Makino et al., 2016),

inducible nitric oxide synthase (iNOS) (Luoma et al.,

1998), glutathione peroxidase (GPx) (Ma et al., 2015) and

et al., 2016).

Cao et al. have showed negative partial correlation

between total anti oxidant status and arterial stiffness

in elderly hypertensive patients that suggests the decline

in antioxidant capacity may be responsible for vascular

in ammation (Vasamsetti et al., 2016).

Roshanak Bayatmakoo et al.

protein kinase (MAPK) is a well known stress-induced

protein kinases in general and subsequent of modi ed

LDLin (Chapple et al., 2013) cells in particular. Studies

and programmed cell death (Brown and Jessup., 1999).

Several plasmatic in ammatory biomarkers have been

cholic acid and tape water .

con rmed by the local institutional animal care anduse

committee (Approval Number:A125345).

Roshanak Bayatmakoo et al.

by the xanthine/xanthine oxidase system.

(randoxLaboratories Ltd.Admore, Northern Ireland, UK).

expressed as nanomolesper milliliter of serum.

antibody (sc-535) and B-actin (sc-47778) then probed

by HRP-conjugated anti-rabbit secondary antibodies

(1:5000;Santa Cruz Biotechnology Inc.) for one hour at

4 °C. The membranes werestripped (Restore Western Blot

Stripping buffer, Pierce Biotechnology, Rockford, IL,

USA). The bandswere detectedusingECL kit (GE Health-

Roshanak Bayatmakoo et al.

(P = 0 .36), the ratios of HDL to LDL were signi cantly

decreased (approximately four times).As shown in table

1 serum OxLDL levels was three times higher in HD

tein, p-p38 MAPK, and proapoptotic protein,c-caspase

Roshanak Bayatmakoo et al.

As shown in (Fig. 2A,B, C) signi cant, moderate and

reverse correlation were found between SOD activity

and expression of c-caspase 3 ( r=-0.62, p<0.01) and

pP38MAPK (r=-0.593, p <0.016),where as positive cor-

relation was observed between SOD activity and expres-

sion of Bcl2(r= 0.593, p<0.016).

Considration of the relationship between GPx activ-

Roshanak Bayatmakoo et al.

When the association of TAC with c-caspase 3,

pP38MAPK were considered, it was noted that the corre-

The strongest also positive correlation was observed

between the levels of circulating MDA and expres-

sion ofc-caspase 3 (r= 0.873, p < 0.000) (Fig. 5A) and

(Fig. 5C).

Atherosclerosis was believed as a simple accumulation

Roshanak Bayatmakoo et al.

in ammatory disease but there is growing evidence

et al., 2000) and central obesity (Verreth et al., 2004)

culating indexes to monitoring of arterial in amma-

tion or apoptosis regarding to association of between

them.

The current study is the  rst in vitro work which

including TAC, SOD, GPx, MDA, OxLDL respectively

re ect arterial in ammation and apoptosis status

accessed by the expression of pP38MAPK, c-caspase

3 and bcl2 in carotid arteries of hyper cholestrolemic

model rats. In this experiment, we made a moderate ath-

terol (TC = 229.35±13.26 mg/dl) We used this model to

Roshanak Bayatmakoo et al.

investigate the expression of in ammation and apop-

serum of hypercholestrolemic rats in comparison to nor-

mal control group. Further the study shows the decrease

in the serum levels of TAC, AIP and activity of anti-

oxidant enzymes containing SOD and GPx which is also

con rmed by (Lluis et al., 2013).

The results indicated the strongest relationship

between the serum levels of MDA and the expression

of pP38MAPK, c-caspase 3or bcl2, suggesting a role

dative stress (Levitan et al., 2010). Since we did not  nd

in ammatory cytokines.