miR-223-3p suppresses inflammation to protect cardiomyocytes by targeting NLRP3 in acute myocardial infarction patients

WANG, Fangfang; CHEN, Xin; SONG, Ying; HUANG, Shenglan; ZHOU, Changle; HUANG, Changgen; CHEN, Zengguang; ZHANG, Liangfeng; JI, Yuan

doi:10.1590/fst.25020

Fangfang WANG

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Xin CHEN

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Ying SONG

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Shenglan HUANG

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Changle ZHOU

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Changgen HUANG

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Zengguang CHEN

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Liangfeng ZHANG

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

Yuan JI ^* * Corresponding author: jyanjmu@163.com

Department of Cardiovascular Disease, Changzhou No.2 People’ s Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu Province, China

http://orcid.org/0000-0002-2509-8505

* Corresponding author: jyanjmu@163.com

Figures (5)
Tables (2)

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Figure 1
miR-223-3p expression in the circulating of AMI, UA and Health group. (A-B) miR-223-3p was high expression in the serum (A) or PBMC (B) of patients with AMI (n = 53) which was compared with health people (n = 53) or UA patients (n = 53).

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Figure 2
Circulating miR-223-3p was negatively correlated with serum myocardial enzyme in AMI. A-D, Serum miR-223-3p expression was negatively correlated with serum CK-MB (A), cTnI (B), AST (C) and LDH (D) levels in AMI patients; E-H, The expression of miR-223-3p in PBMC was negatively correlated with serum CK-MB (E), cTnI (F), AST (G) and LDH (H) levels in AMI patients.

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Figure 3
Circulating miR-223-3p was negatively correlated with serum inflammatory factor in AMI. A-D, Serum miR-223-3p expression was negatively correlated with serum TNF-α (A), IL-6 (B), IL-1β (C) and IL-8 (D) levels in AMI patients; E-H, The expression of miR-223-3p in PBMC was negatively correlated with serum TNF-α (E), IL-1β (F), IL-6 (G) and IL-8 (H) levels in AMI patients.

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Figure 4
miR-223-3p regulated inflammation in PBMC by targeting NLRP3. (A) Sequence in which NLRP3 and miR-223 are combined; (B) miR-223-3p-NC/miR-223-3p-mimic/miR-223-3p-inhabitor were transected into THP-1 cells, and luciferase activity was detected (Perform 3 independent replicate experiments); (C) miR-223-3p was negatively correlated with NLRP3 mRNA in PBMC of AMI patients (n = 53); (D) RT-qPCR was used to detect the expression of miR-223-3p in PBMC of healthy people (n = 10); (E) The content of IL-1β in culture medium for PBMC of 10 cases healthy people; (F) RT-qPCR was used to detect the expression of NLRP3 mRNA in PBMC of healthy people (n = 10) (Perform 3 independent replicate experiments); (G) Western blot was used to detect the expression of NLRP3 mRNA in PBMC of healthy people (n = 10) (Perform 3 independent replicate experiments). Compared with miR-223-3p-NC, *** was P < 0.001.

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Figure 5
IL-1β induced the apoptosis of cardiomyocytes in a dose-dependent. (A-E) Flow cytometry was used to detect the apoptosis of H9C2 cells with 0 (A), 2 (B), 4 (C), 8 (D) and 16 (E) ug/L IL-1β; (F) Statistical analysis of apoptosis in H9C2 cells (3 independent repeats per experiment).

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Table 1
Comparison of clinical data of the three groups of study subjects.

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Table 2
Results of the logistic regression analysis.

Variables	No-AMI		AMI	Probability value
Variables	Health	UA	AMI	Probability value
Number (cases)	53	53	53	not applicable
Age (year)	60.2 ± 7.9	59.6 ± 9.0	60.8 ± 8.2	0.674
male (n/%)	32/60.4	36/67.9	35/66.0	0.623
Smoking (n/%)	27/50.9	26/49.1	29/54.7	0.398
Hypertension (n/%)	20/37.7	22/41.5	21/39.6	0.428
TC (mmol/L)	3.98 ± 0.72	4.08 ± 0.93	4.19 ± 0.92	0.366
TG (mmol/L)	1.45 ± 0.83	1.51 ± 0.89	1.53 ± 1.06	0.471
HDL-C (mmol/L)	1.22 ± 0.84	1.19 ± 0.92	1.12 ± 0.89	0.209
LDL-C (mmol/L)	2.35 ± 0.92	2.42 ± 0.62	2.52 ± 0.67	0.513
CK-MB (U/L)	15.3 ± 4.2	15.5 ± 6.8	136.0 ± 76.9	<0.001
cTnI (ug/L)	0.12 ± 0.06	0.34 ± 0.11	54.9 ± 28.6	<0.001
AST (U/L)	30.9 ± 3.9	33.6 ± 8.3	69.8 ± 14.7	<0.001
LDH (U/L)	156.8 ± 22.4	165.1 ± 36.4	687.4 ± 242.2	<0.001
TNF-α (ng/L)	75.9 ± 26.4	142.3 ± 80.2	275.2 ± 109.3	<0.001
IL-6 (ng/L)	12.1 ± 6.8	35.2 ± 19.3	73.3 ± 30.8	<0.001
IL-1β (ng/L)	21.8 ± 10.5	46.9 ± 25.1	112.8 ± 32.8	<0.001
IL-8 (ng/L)	20.4 ± 7.3	45.3 ± 19.2	98.1 ± 30.9	<0.001

Variables	B	S.E.	Wald	Sig.	Exp (B)	95% CI
Age (year)	0.151	0.052	2.675	0.112	0.942	0.909-1.010
male (n/%)	-0.895	0.610	1.752	0.171	2.402	0.615-9.063
Smoking (n/%)	3.102	0.416	6.034	0.006	1.112	0.356-3.374
Hypertension (n/%)	-0.166	0.341	0.143	0.235	0.706	0.236-2.215
TC (mmol/L)	0.321	0.621	0.308	0.414	0.204	0.211-2.371
TG (mmol/L)	-1.015	0.521	3.514	0.061	0.338	0.109-1.051
HDL-C (mmol/L)	-0.107	0.148	0.508	0.439	1.037	0.945-1.139
LDL-C (mmol/L)	0.053	0.203	0.002	0.968	0.997	0.847-1.172
CK-MB (U/L)	0.162	0.784	0.139	0.130	0.754	0.187-3.076
CTnI (ug/L)	0.245	1.063	0.458	0.025	2.087	0.265-16.426
AST (U/L)	0.631	1.820	0.047	0.102	2.291	0.009-564.45
LDH (U/L)	1.242	2.719	0.812	0.068	4.621	0.162-131.75
TNF-α (ng/L)	8.523	3.020	4.522	0.043	0.350	0.000-0.508
IL-6 (ng/L)	5.614	2.250	3.017	0.083	3.349	0.488-20.646
IL-1β (ng/L)	0.251	0.038	5.223	0.032	1.210	1.144-1.278
IL-8 (ng/L)	2.312	1.258	3.125	0.059	1.258	0.982-1.324
PBMC miR-223-3p	-2.124	0.792	7.301	0.005	8.210	1.784-38.214
Serum miR-223-3p	-1.592	0.625	5.012	0.008	9.236	2.354-26.371

[1] * Corresponding author: jyanjmu@163.com

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miR-223-3p suppresses inflammation to protect cardiomyocytes by targeting NLRP3 in acute myocardial infarction patients

Abstract