**Notes/thanks/other declarations**

*Apolipoproteins, Triglycerides and Cholesterol*

LDL-R knockout mice and diabetic mice [218, 219].

miR-33 also lowers VLDL-TG contents in nonhuman primates [216]. Furthermore, anti-miR-33 therapy inhibits the gene expressions that enhance mitochondrial respiration and ATP production, promotes macrophage cholesterol efflux accompanying with ABCA1 upregulation, and reduces atherosclerosis [217]. In addition, miR33 inhibition overcomes the deleterious effects of atherosclerosis plaque progression in

Additionally, inhibiting miR-144 could upregulate hepatic ABCA1 expression and increase HDL-C levels through the FXR-dependent pathway [220]. However, overexpression of miR-144 in the liver reduces ABCA1 expression, attenuates cholesterol efflux in macrophages, reduces HDL-C levels, and promotes atherosclerosis development [221]. An increase in miR-145 decreases ABCA1 expression and reduces plasma HDL-C levels and glucose-stimulated insulin secretion in islets. However, inhibiting miR-145 produces the opposite effects of increasing ABCA1 expression, promoting HDL biogenesis in the liver and improving glucose-stimulated insulin secretion in islets [222]. In mice, inhibition of miR-148a increases the hepatic expression of LDL-R and ABCA1, subsequently decreases plasma LDL-C concentrations, and elevates HDL-C levels, which may decrease LDL-C/HDL-C ratio and CVD risk [223]. Furthermore, miR-185, miR-96, and miR-223 may repress selective HDL-C uptake through inhibiting hepatic SR-BI, implying a novel mode of SR-BI regulation and an important role of miRNAs in modulating cholesterol metabolism [224]. Thus, these findings strongly supported the idea of developing miRNA inhibitors for the treatment of dyslipidemia and atherosclerosis [225].

As the failure of CEPT inhibitors on reducing CVD risk, the traditional concept of HDL against CVD from Framingham study has been challenged. Besides, abnormal HDL functions in the setting of systemic diseases also make HDL more confused to be understood. Consequently, whether HDL-C is still a good predictor for CVD and whether HDL could really provide valuable protections against CVD are questioned. HDL comprises a heterogeneous group of particles composed of various of bioactive components. The compositional complexity of HDL is almost hardly to be reflected by measuring cholesterol contents loading in HDL. Thus, quantifying HDL-P numbers and evaluating HDL functions might be the more meaningful markers for CVD prediction. Meanwhile, many emerging strategies targeted to regulate HDL metabolism and increase HDL-P levels were also attempted. Expectedly, more available measurement methods and therapeutic agents about

This project was supported by grant 31200884 from the National Natural Science Foundation of China; by grant 2018Y9100 from the Joint Funds for the Innovation of Science and Technology, Fujian Province; and by grant 2019HSJJ04 from highlevel hospital foster grants of Fujian Provincial Hospital, Fujian Province, China.

The author declares that there are no conflicts of interest.

**26**

**9. Conclusions**

HDL would arise in the near future.

**Acknowledgements**

**Conflict of interest**

I thank Dr. Yansong Guo and Dr. Na Lin for the kind help on editing and polishing this manuscript.
