Novel caffeic acid derivatives promote the phenotypic and functional switch of macrophages toward resolution of inflammation and cardiac regeneration after myocardial infarction


Grant Data
Project Title
Novel caffeic acid derivatives promote the phenotypic and functional switch of macrophages toward resolution of inflammation and cardiac regeneration after myocardial infarction
Principal Investigator
Dr Rong, Jianhui   (Principal investigator)
Co-Investigator(s)
Dr Li Xuechen   (Co-Investigator)
Professor Han Yi Fan   (Co-Investigator)
Duration
36
Start Date
2015-11-01
Completion Date
2018-10-31
Amount
1059311
Conference Title
Presentation Title
Keywords
myocardial infarction, macrophages, caffeic acid derivative, Nrf2/HO-1, iNOS
Discipline
Traditional Chinese Medicine (basic)
Panel
Biology and Medicine (M)
Sponsor
RGC General Research Fund (GRF)
HKU Project Code
17120915
Grant Type
General Research Fund (GRF)
Funding Year
2015/2016
Status
On-going
Objectives
2 The second objective is to discover the mechanisms by which PACA regulates the phenotypic and functional switch of macrophages. iNOS is a useful biomarker for monitoring the phenotypes and functions of macrophages. We recently found that PACA activated Nrf2 pathway and induced antioxidant HO-1 via direct modification of Keap1. We also found that HO-1 inhibitor could attenuate the inhibitory effect of PACA on iNOS induction. Thus, this study will focus on the effect of PACA on iNOS as an indicator. We will employ siRNA, ChIP, promoter cloning and promoter-reporter system to address how different transcription factos and signaling pathways (i.g., PKC, PKA, COCS-1 and -3) regulate the expression of iNOS in response to PACA. 3 The third objective is to explore the in vivo efficacy of PACA in modulating pro-inflammatory and anti-inflammatory macrophages in rodent MI models. We found that PACA attenuated isoproterenol-induced myocardial injury by reducing NO production and increasing GSH levels. On the other hand, PACA effectively stimulated macrophages to secret chemotactic mediators for bone marrow-derived hematopoietic stem cells. Thus, we will verify whether PACA exhibits cardioprotective activity in rodent MI models by targeting macrophages. We will focus on the in vivo effects of PACA on phenotypes and functions of macrophages with a special regard to resolution of inflammation and cardiac repair.