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. 2019 Aug 21:12:1543-1553.
doi: 10.2147/DMSO.S219013. eCollection 2019.

Therapeutic targets of hypercholesterolemia: HMGCR and LDLR

Shizhan Ma  1   2 , Wenxiu Sun  3 , Ling Gao  1   4   5 , Shudong Liu  6
Affiliations

Therapeutic targets of hypercholesterolemia: HMGCR and LDLR

Shizhan Ma et al. Diabetes Metab Syndr Obes. .

Abstract

Cholesterol homeostasis is critical and necessary for the body's functions. Hypercholesterolemia can lead to significant clinical problems, such as cardiovascular disease (CVD). 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and low-density lipoprotein cholesterol receptor (LDLR) are major points of control in cholesterol homeostasis. We summarize the regulatory mechanisms of HMGCR and LDLR, which may provide insight for new drug design and development.

Keywords: CVD; HMGCR; LDLR; cholesterol homeostasis.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic diagram of cholesterol metabolic pathway in the body.
Figure 2
Figure 2
Control point of HMGCR. Abbreviations: HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; SRE, Sterol regulatory element; ER, endoplasmic reticulum; SREBP, sterol regulatory element binding protein; SCAP, SREBP cleavage activating protein; AMPK, AMP-activated protein kinase; PKC, Protein kinase C; CaMK, Ca2+/calmodulin-dependent protein kinase; ERAD, ER-associated degradation; 25-OH cholesterol, 25-hydroxycholesterol; RNF145, ring finger protein 145.
Figure 3
Figure 3
Control point of LDLR. Abbreviations: LDLR, low–density lipoprotein cholesterol receptor; SREBP, sterol regulatory element binding protein; IDOL, inducible degrader of the LDLR; PCSK9, proprotein convertase subtilisin/kexin type 9; LXR, Liver X receptors; R1, repeat 1 sequence; R2, repeat 2 sequence; R3, repeat 3 sequence; ERα, estrogen receptor α.
Figure 4
Figure 4
Schematic diagram of the hypercholesterolemia and current therapeutic drug. PCSK9 inhibitor: proprotein convertase subtilisin/kexin type 9 inhibitor. Abbreviations: LDL, low–density lipoprotein; LDLR, low–density lipoprotein cholesterol receptor.
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