Effects of peripheral blood VEGFR-3+ monocytes on left ventricular remodeling in mice with hypertension

doi:10.11958/20221051

Abstract

Abstract:

Objective To explore the effects of peripheral blood VEGFR-3⁺monocytes (PBMV) on left ventricular (LV) remodeling induced by high salt intake. Methods Six-week-old male C57BL/6 mice were randomly divided into the 0.5% NaCl concentration diet (W/W, normal salt, NS) group, the 8% NaCl concentration diet (W/W, high salt, HS) group, the HS+ N-nitro-L-arginine methyl ester (L-NAME, HS+L) group and the HS+L+PBMV treatment group. PBMV intervention was performed in hypertensive mice from 9-12 weeks after high salt diet intervention. Noninvasive tail pressure was measured by standard tail pressure method in all mice. Cardiac structure and function were determined using a Vevo 2100 ultrasound imaging system. The mRNA levels of tonicity responsive enhancer binding protein (TonEBP) and lymphatic endothelial cell markers in mouse myocardial tissue were detected by fluorescence quantitative PCR. Masson staining was used to observe the degree of myocardial fibrosis. Calculation of cardiomyocyte cross-sectional area (CSA) was analyzed by fluorescence staining of malt germ lectin (WGA). Results At the end of the intervention, the systolic pressure (SBP) was significantly increased in the HS+L group compared with the other groups (P<0.05). The mRNA levels of TonEBP was significantly lower while the lymphatic endothelial cell markers of VEGF-C, Prox-1, Podoplanin and LYVE-1 were significanly higher in the HS+L+PBMV group than those of the HS+L group (P<0.05). Echocardiography measurement demonstrated that the LV end-diastolic dimension (LVEDD) and LV posterior wall thickness (LVPWT) were significantly decreased in the HS+L+PBMV group than those of the HS+L group. The LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were significantly increased in the HS+L+PBMV group compared with those of the HS+L group (P<0.05). The pathological results showed that the CVF and CSA were significantly decreased in the HS+L+PBMV group than those of the HS+L group (P<0.05). Conclusion The present study demonstrates that PBMV treatment can reduce SBP and ameliorate LV remodeling in hypertensive mice, which may be related to promoting lymphangiogenesis.

Key words: hypertension, ventricular remodeling, vascular endothelial growth factor receptor-3, monocytes, lymphangiogenesis, flow cytometry, high salt

CLC Number:

R544.11

Figures/Tables 9

References 16

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基因名称	引物序列（5'→3'）	产物大小（bp）
β-actin	上游：CTAAGGCCAACCGTGAAAAG	104
β-actin	下游：ACCAGAGGCATACAGGGACA	104
Prox-1	上游：ATACCGAGCCCTCAACATGC	87
Prox-1	下游：CGTAACGTGATCTGCGCAAC	87
LYVE-1	上游：GGCTTTGAGACTTGCAGCTATG	177
LYVE-1	下游：GCAGGAGTTAACCCAGGTGT	177
Podoplanin	上游：TGGCAAGGCACCTCTGGTA	77
Podoplanin	下游：TGAGGTGGACAGTTCCTCTAAGG	77
VEGF-C	上游：GTTACAGAAGACCGTGTGCGAATC	85
VEGF-C	下游：GATGGGACACAGCGGCATA	85
TonEBP	上游：TTCATAGTTGGAATTTCAGAGCA	153
TonEBP	下游：TTGCGAGTATACAAATGTTCCAA	153

基因名称	引物序列（5'→3'）	产物大小（bp）
β-actin	上游：CTAAGGCCAACCGTGAAAAG	104
β-actin	下游：ACCAGAGGCATACAGGGACA	104
Prox-1	上游：ATACCGAGCCCTCAACATGC	87
Prox-1	下游：CGTAACGTGATCTGCGCAAC	87
LYVE-1	上游：GGCTTTGAGACTTGCAGCTATG	177
LYVE-1	下游：GCAGGAGTTAACCCAGGTGT	177
Podoplanin	上游：TGGCAAGGCACCTCTGGTA	77
Podoplanin	下游：TGAGGTGGACAGTTCCTCTAAGG	77
VEGF-C	上游：GTTACAGAAGACCGTGTGCGAATC	85
VEGF-C	下游：GATGGGACACAGCGGCATA	85
TonEBP	上游：TTCATAGTTGGAATTTCAGAGCA	153
TonEBP	下游：TTGCGAGTATACAAATGTTCCAA	153

组别	基线	8周	12周
NS组	113.13±4.82	115.13±5.69	113.25±4.33
HS组	114.25±4.17	134.63±4.57^a	136.63±13.05^a
HS+L组	112.25±4.23	137.13±6.24^a	152.88±19.36^ab
HS+L+PBVM组	113.63±3.11	138.00±13.71^a	138.50±7.07^ac
F	0.335	13.380^＊＊	12.850^＊＊

组别	基线	8周	12周
NS组	113.13±4.82	115.13±5.69	113.25±4.33
HS组	114.25±4.17	134.63±4.57^a	136.63±13.05^a
HS+L组	112.25±4.23	137.13±6.24^a	152.88±19.36^ab
HS+L+PBVM组	113.63±3.11	138.00±13.71^a	138.50±7.07^ac
F	0.335	13.380^＊＊	12.850^＊＊

组别	TonEBP	VEGF-C	Prox-1	Podoplanin	LYVE-1
NS组	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
HS组	2.17±0.27^a	1.88±0.41^a	2.77±0.48^a	2.33±0.64^a	2.69±0.49^a
HS+L组	2.87±0.82^a	1.80±0.40^a	2.56±0.45^a	2.41±0.49^a	2.88±0.55^a
HS+L+PBVM组	2.35±0.72^a	3.16±0.55^abc	3.73±0.34^abc	3.95±0.46^abc	4.38±1.03^abc
F	5.906^＊	15.260^＊＊	28.360^＊＊	20.400^＊＊	14.330^＊＊