Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes

Abstract

Background Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. Material/Methods In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N -nitro-l-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. Results The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6C hi monocytes was significantly decreased while that of Ly6C lo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. Conclusions Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.

MK2 deficiency decreases mortality during the inflammatory phase after myocardial infarction in mice

“…This study would have missed changes in neutrophil recruitment, which peaks 1-day post-MI, and would not discriminate between Ly-6C hi and Ly-6C lo monocytes, which peak on day-3 and day-7 post-MI, respectively 30 . Ly-6C hi monocytes are pro-inflammatory whereas Ly-6C lo monocytes have been implicated in resolving the inflammatory response 30,[90][91][92] . In an inflammatory environment such as the infarct zone, monocytes differentiate into macrophages, supplementing the complement of resident macrophages 93,94 .…”

HNP-1 Reverses Hypertensive Left Ventricular Hypertrophy by Inhibiting the NF-кB Signaling Pathway

“…Second, HNP-1 may have a "bipolar effect," such that inflammatory factor expression may be enhanced by a high dose of HNP-1 (100 μg/day) and inhibited by a healthy dose of HNP-1 (5 μg/day or 10 μg/mL) [65]. Third, studies have reported that regulation of the inflammatory response effectively controls BP and ameliorates HLVH [65][66][67][68][69][70][71]. However, NF-κB is a key regulatory signaling pathway in inflammatory immune responses [72][73][74][75], and NF-κB inhibition may ameliorate hypertension and HLVH [76][77][78][79][80][81][82][83][84][85][86].…”

Macrophage Polarization in Left Ventricular Structural Remodeling Induced by Hypertension

“…A long-term high-salt diet can induce hypertension and myocardial hypertrophy. In animal models, mice on a high-salt diet developed left ventricular hypertrophy and reduced cardiac contractile function [ 16 , 17 ].…”

“…Yu et al . [ 17 ] intervened in mice for 12 weeks with a diet containing 8% NaCl or a combination of 8% NaCl diet and intraperitoneal injection of N-nitro-L-arginine methyl ester (10 mg/mL, 50 mg/kg/d). In the combined intervention group, the expression of M1 correlation factors such as TNF- , CCL-2, IL-1 , and CCL-5, and M2 correlation factors Ym-1, Arg-1, and IL-10 were significantly increased at the mRNA level.…”