Dai, Jinjie

Fang, Weiyi

Min, Zhang

Qu, Xinkai

Xu, Lei

Yang, Yiqing

Elsevier - Publisher Connector 

membrane potential, citrate synthase activity and mtDNA copy number (P<0.05).
Furthermore, HG cells showed decreased SIRT1 expression and PGC-1a acetylation.
Additionally, mRNA and protein expression of PGC-1a downstream genes (NRF-1,
NRF-2, ERR-a and TFAM) were reduced in HG group. Resveratrol reversed these
changes in HG group, but this effect was diminished in HG+ sh-SIRT1 group.
Conclusions: Resveratrol protects against cardiac apoptosis and improves cardiac
function in diabetic mice through enhancing mitochondrial biogenesis and function.
SIRT1 plays an important role in the resveratrol beneﬁcial effects against diabetic
cardiomyopathy.
GW25-e4357
Ghrelin receptor deﬁciency aggravates instability of atherosclerotic plaque and
vascular inﬂammation in low-density lipoprotein receptor-null mice
Zhang Min, Xinkai Qu, Yiqing Yang, Lei Xu, Jinjie Dai, Weiyi Fang
Department of Cardiology, Shanghai ChestHospital, Shanghai Jiaotong University,
Shanghai, 200030, China
Objectives: Ghrelin has been found to be associated with anti-inﬂammation, inhibi-
tion of atherosclerotic plaque formation and plaque stability in cardiovascular system.
We investigated whether ghrelin affected the atherosclerotic plaque and immune
inﬂammation of atherosclerosis.
Methods: We crossed ghrelin receptor knock out mice (GHSR-/-) into a low-density
lipoprotein receptor-null (LDLR-/-) mouse line. In this model, atherosclerotic lesions
were promoted by feeding a high-fat, high-cholesterol Western-type diet for 18 weeks,
following a standard protocol. Serum lipid levels, atherosclerotic plaque on aortic
arches, and the expression of ICAM-1 and VCAM-1, T cell, macrophage and smooth
muscle cell of atherosclerotic plaque were observed.
Results: Though the serum lipid levels and atherosclerotic plaque area on aortic arches
were not signiﬁcantly different between in GHSR+/+/LDLR-/- mice and GHSR
-/-LDLR-/- mice, the protein expression of ICAM-1 and VCAM-1 in atherosclerosis
plaque were increased in GHSR -/-LDLR-/- mice than that in GHSR+/+/LDLR-/- mice.
T cell and macrophage were more, while the smooth muscle cells of atherosclerosis
plaque were less in GHSR -/-LDLR-/- mice than that in GHSR+/+/LDLR-/- mice.
Conclusions: In conclusion, ghrelin receptor deﬁciency aggravates instability of
atherosclerotic plaque and vascular inﬂammation but not atherosclerotic plaque area,
which will provide novel avenues for the treatment of atherosclerosis patients.
GW25-e4400
Study on the relationship between the serum level of GDF15a and infarction area
for rats with myocardial infarction
Bin Wang1, Xia Yu2, Guodong Liang1
1Jilin Tumor Hospital, 2the First Hospital of Jilin University
Objectives: Through detecting the serum level of growth differentiation factor 15a
(GDF 15a) of the rats with different myocardial infarction area, to explore the rela-
tionship between the serum level of GDF15a and myocardial infarction area and the
prediction effect of GDF15a on myocardial infarction area.
Methods: 1. Experimental animals: 30 healthy Wistar rats, male, weighing 200w300
g, are selected. Rats are randomly divided into high ligation group, low ligation group
and sham operation group with 10 rats in each group. 2. Myocardial infarction model
set up: Rats are injected with 10% chloral hydrate and ﬁxed on the operation board,
assisted respiration with endotracheal intubation, connected to electrocardiograph
(ECG) and monitored. In high ligation group, the coronary arteries of rats are ligated
about 3mm from the aortic root which is between the left atrial and pulmonary arterial
cone. In low ligation group, the coronary arteries are ligated about 2 mm from the tip
of left atrial appendage. Method used in sham operation group is similar to low
ligation group but without coronary artery ligation. Penicillin is applied in order to
prevent postoperative infection. 3. Rats serum GDFl5a detection: 2ml blood sample is
taken from the abdominal aorta of each rat in 24h after operation, GDFl5a is then
detected using ELISA method. 4. Infarction area computation: Each rat is sacriﬁced
after blood sampling, heart is harvested, the left ventricular long axis transverse
segment which is below the left coronary artery ligation point is collected and
sectioned, the thickness of the slices is 4mm. The slices are then HE stained and used
to do heart-pathological monitoring and compute infarction area. Infarction area (%)¼
[(The endocardial length of the left ventricular infarct / Total endocardial circumfer-
ence) /2 + (The epicardial length of the left ventricular infarct / Total epicardial
circumference) /2] 100%. Calculation is implemented by the professional image
analysis software IPP 6.0. 5. Statistical method: Measurement results are showed in
the manner of averagestandard deviation (SD), ANOVA and t test are applied to
calculate statistical signiﬁcance, all analysis are done using statistical software
SPSS 17.0.
Results: Three rats in high ligation group are dead in 24h after operation compared to
one rat in low ligation group. Result 1: Serum GDFL5a detection results for each
group: the contents of GDFL5a are respectively 1190.261.4ng/L in high ligation
group, 931.693.0ng/L in low ligation group and 637.261.2ng/L in sham operation
group. ANOVA result for the average comparison of three groups is F¼117.8 with
P<0.001, which shows that this result has statistical meaning and the content of
GDFl5a in high ligation group is signiﬁcantly higher than the ones in low ligation
group and sham operation group. Result 2: Computation of infarction area between
three groups: The infarction areas are respectively 57.74.0 in high ligation group,
38.64.6 in low ligation group and 0 in sham operation group. T-test is applied to
compare the areas between high ligation group and low ligation group, t¼8.7 withJACC Vol 64/16/Suppl C j October 16–19, 2014 j GW-ICC Abstracts/BP<0.001, which shows that this result also has statistical meaning and infarction area
in high ligation group is signiﬁcantly larger than the one in low ligation group.
Conclusions: The serum level of GDFl5a rises for the rats with cardiac obstruction, its
level rises with an increasing infarction area, this phenomenon shows that the serum
level of the GDFl5a has certain prediction effect on the infarction area.
GW25-e4408
Magnolol administration in prehypertension postpones the development of
hypertension and the underlying mechanisms
Xiangyan Liang1, Wenjuan Xing2, Jinxiao He3, Fange Liu1, Feng Gao2,
Haifeng Zhang1
1Experiment Teaching Center, Fourth Military Medical University, 2Department of
Physiology, Fourth Military Medical University, 3Department of Pediatrics, Xijing
Hospital, Fourth Military Medical University
Objectives: Patients with prehypertension are more likely to progress to manifest
hypertension than those with optimal or normal blood pressure. However, the
mechanisms underlying the development from prehypertension to hypertension still
remain largely elusive and the drugs for antihypertensive treatment in prehypertension
are absent. Here we determined the effects of magnolol (MAG) on blood pressure and
aortic vasodilatation to insulin, and investigated the underlying mechanisms.
Methods: Four-week-old male spontaneous hypertensive rats (SHR) and age-matched
normotensive Wistar-Kyoto (WKY) control rats weretreated with vehicle (distilled
water) or MAG (100 mg/kg/day, o.g., once daily) for 3 weeks. Additionally, human
umbilical vein endothelial cells (HUVECs) were exposed to glucose (25 mmol/L) and
saturated FFA palmitate (16:0; 500 mmol/L) (HG/HF) for 18 hours and treated with
MAG (10mmol/L) for 48 hours.
Results: MAG signiﬁcantly decreased blood pressure in seven-week-old SHR (SBP:
1316 vs. 16011 mmHg in vehicle-treated SHR, DBP: 1065 vs. 1278 mmHg,
n¼8, P<0.01), improved insulin-induced aorta vasodilation (relaxation: 57.4%2.4%
vs. 42.2%5.3%, n¼6, P<0.01), restored Akt and eNOS phosphorylations stimulated
by insulin, and increased PPARg and decreased TRB3 expressions (n¼5-6, P<0.05).
Furthermore, in cultured HUVECs, MAG incubation increased PPARg, decreased
TRB3 expressions, and restored insulin-induced phosphorylated Akt and eNOS levels
and NO production (P<0.05), which was blocked by both PPARg antagonist and
siRNA targeting PPARg (P<0.05).
Conclusions: Treatment of young SHRs with MAG beginning at the prehypertensive
stage decreases blood pressure via improving vascular insulin resistance, which is at
least partly attributable to upregulated PPARg, downregulated TRB3 and conse-
quently increased Akt and eNOS activations in blood vessels. These results indicate
that MAG may be used as an antihypertensive drug early administrated at the pre-
hypertensive stage.
GW25-e4516
Genotype-phenotype analysis on a large cohort of Chinese LQTS patients
Gao Yuanfeng1, Wenling Liu1, Li Zhang2, Dayi Hu1, Cuilan Li1
1Heart Center, Peking University People’s Hospital, Beijing, 100044, P.R.China,
2Lankenau Medical Center, Lankenau Institute for Medical Research, Jefferson
Medical College, Philadelphia, PA, U.S.A.
Objectives: Long QT syndrome (LQTS) is an inherited cardiac disorder characterized
by syncope or even sudden death. Although a variety of clinical index could point to a
diagnosis of LQTS, gene-screening remains to be the golden standard for LQTS
diagnosis. In addition, while 15 genes have been identiﬁed as LQTS causing
genes, 90% of the mutationslie mainly in KCNQ1, KCNH2, SCN5A– the causing
genes of LQT1-3. So, in the present study, we aim to evaluate the diagnostic value of
the clinical data by analyzing the genetically diagnosed LQTS patients. Besides, we
also investigated the mutation spectrum and gene distribution of Chinese LQTS
patients.
Methods: 214 LQTS patients, selected from the Chinese Channelopathy Registry
Study, were enrolled into this study. Patients were evaluatedbased on QTcandclinical
manifestations. Individuals were clinically diagnosed as LQTS if presenting a pro-
longed QT interval (QTc450ms for male; QTc470ms for female) and/or docu-
mented TdP (Torsade de Pointes), ventricular ﬁbrillation as well as cardiac arrest.
Mutational screening of KCNQ1, KCNH2, SCN5A genes was performed by PCR
and direct DNA sequence analysis. LQTS phenotype were evaluated for all putative
LQTS patients.
Results: For the total cohort of the LQTS patients, 173 patients were genotype-pos-
itive for LQTS, while 41 negative. We compared the phenotypes between the two
groups. Statistical results indicate that differences of average QTc, Schwartz score,-
percentages of patients with syncope, and Schwartz score>4 between the two groups
are signiﬁcant (P<0.05), while those of age of ﬁrst syncope, gender (female vs. male),
percentages of patients with QTc>480ms and TdP not (P>0.05).
Overall, 173 of 214 (81%) LQTS patients were found to harbor at least one putative
LQTS-causing mutation. Among them, 99 mutations were identiﬁed: 42 were in
KCNQ1, 54 in KCNH2, 3 in SCN5A. In this set of mutations, 42 were novel, including
15 in KCNQ1, 27 in KCNH2, and none in SCN5A. To be speciﬁc, most of mutations
(71 of 99, 72%) were missense, while frame-shift mutations, splice sites, nonsense and
inframe deletions account for 15% (15/99), 5% (5/99), 5% (5/99), 2% (2/99), respec-
tively.Most frameshift mutations (11 of 15, 73%) were found in KCNH2 (representing
20% of all KCNH2mutations), while 80% (4/5) of the splice mutations were identiﬁedasic and Translational Medicine C25


GW25-e4357 Ghrelin receptor deficiency aggravates instability of atherosclerotic plaque and vascular inflammation in low-density lipoprotein receptor-null mice 

file:///data/remote/core/dit/data/elsevier/pdf/e9b/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMDczNTEwOTcxNDAzMDE2Mg==.pdf

GW25-e4357 Ghrelin receptor deficiency aggravates instability of atherosclerotic plaque and vascular inflammation in low-density lipoprotein receptor-null mice

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector