Table 1.
HDL as a therapeutic tool.
| Disease studied | Method | HDL-intervention | Conclusions | PMID | |
|---|---|---|---|---|---|
| Cardio-metabolic Diseases | Acute Coronary Syndrome | Human | Autologous delipidated serum diffusion | Well-tolerated in patients with ACS | 20538165 |
| Human | CER-001 | Treatment did not reduce coronary atherosclerosis | 24780501 | ||
| Human | CSL112 | Repeated infusions were safe and well-tolerated | 24122814 | ||
| Coronary Artery Disease | Human | MDCO-216 | ↑ atherogenic lipid profile (unexpected) (27816804), ↑ apoA1, ↑ phospholipids, ↑ pre-β HDL, at high doses (>20 mg/mL) ↑ TG, ↓ HDL-C (27418968) | 27816804, 27418968 |
|
| Human | CSL112 | ↑ apoA1, ↑ cholesterol efflux, ↑ pre-β HDL | 24969776 | ||
| Mouse and human | HDL-CAD loaded with S1P | Restored HDL function (vasodilatation in ex-vivo myograph mouse aorta), restored ERK and Akt signaling | 26403344 | ||
| Myocardial Ischemia | Rat | rHDL VEGF | Efficient delivery of VEGF, 13% ↑ of ejection fraction over controls | Sun et al. (85) | |
| Type 2 Diabetes Mellitus | Human | Extended release niacin therapy | ↑ improves HDL vaso-protective properties, ↓ oxidation and ↑ NO production | 20026785 | |
| Human | Pioglitazone administration | ↓ oxHDL, HDL-C remain constant (30740640), ↓HDL-T (25137425) | 30740640, 25137425 |
||
| Human | RVX-208 | Δ HDL lipidome, HDL-C remain constant | 27173469 | ||
| Mouse | HDL infusion | ↓ plasma glucose, ↓ inflammation, ↑ muscle glycogen, ↑ pancreatic islet structure (23166092), ↑ glycemic control, ↑ insulin sensitivity, ↑ glucose uptake into muscle, ↑ glucose disposal, ↑ glucose phosphorylation (27193916) | 23166092, 27193916 |
||
| Mouse | MDCO-216 | Reversed CV dysfunction and heart failure in T2DM-induced by HSHF diet | 30871282 | ||
| Human | rHDL infusion | ↓ fasting lipolysis, ↓ FA oxidation, ↓ circulating glycerol, ↑ NEFA (21224289), ↑ Cholesterol Efflux, ↑ Anti-inflammatory properties (19281927) | 21224289, 19281927 |
||
| Atherosclerosis | Rabbit and human, in-vitro HCAEC | ETC-642 | Anti-inflammatory effects via inhibiting TNF-α, VCAM-1 ICAM-1, no change in HDL lipid composition (22128776), Anti-inflammatory comparable to native ApoA1, via NFκB inhibition (21571275), Phase-I Clinical Trial showed it was safe and well-tolerated in humans in a range of doses (86) | 22128776, 21571275, Khan et al. (86) |
|
| Rabbit and human | ETC-216 | 6% ↓ soft plaques with ETC-216, 5% ↓with apoA1 Milano and plaque unchanged in placebo group, ↓ macrophage density at plaque (18342230), in humans ↓ mean atheroma volume by 1.06% (14600188) | 18342230, 14600188 |
||
| Human and mouse | CSL111 | ↑ hApoA1, ↑ hpre-β HDL, ↑ total cholesterol, ↑ TG (22067613), ↓ mean atheroma volume by 3.4%, treatment group had abnormal liver function (17387133) | 22067613, 17387133 |
||
| Rabbit and human | CSL112 | ↑ HDL-VS, ↑ efflux capacity in treated compared to native HDL, ↑ ABCA1 dependent efflux | 23868939 | ||
| Human and mouse | CER-001 | ↑ cholesterol elimination, ↓ inflammation, ↓ plaque size, ↓ lipid content of the plaque, 80% ↓ macrophage in plaque (24401224), CHI-SQUARE trial: treatment did not reduce coronary atherosclerosis (24780501), CARAT trial: no reduction of atherosclerotic plaques, no change in plaque composition (28567351) | 24401224, 24780501, 28567351 |
||
| Human | rHDL infusion | ↓ VCAM-1, ↓ plaque lipids, ↓ macrophage size, ↑ HDL-C | 18832751 | ||
| Mouse | ELK-2A2K2E | ↑ Cholesterol Efflux, ↓ Atherosclerosis, ↓ Vascular Inflammation and Oxidation | 23874769 | ||
| Mouse | 4F | ↓ early atherosclerosis lesions, ↓ inflammation, no change in mature atherosclerotic lesions | 20876212 | ||
| Mouse and rabbit | ApoE mimetics | ↑ HDL PON-1 activity, ↓ atherosclerosic lesions, ↓ inflammation | 20221865 | ||
| Mouse, rabbit human cell-lines | rHDL loaded with anti-atherosclerosis drugs | Statin: ↓ inflammation in advances plaques, inhibits progression of inflammation (24445279), | 24445279, 23069716, |
||
| Tanshinone IIA: ↑ anti-atherogenic capacity than drug alone (23069716, 21835236), Atorvastatin and dextran sulfate coat: ↑ delivery of drug to macrophages, ↓ oxLDL uptake (28004910), Lovastatin: Inhibition of oxLDL internalization and ↓ of 50% of intracellular lipid load compared to lovastatin alone (29382194), Simvastatin: ↓ macrophage proliferation, ↓ plaque inflammation, favorable plaque remodeling (26295063), Statins and Hyaluronic Acid (HA) encapsulation: HA encapsulation resulted in ↑ uptake in atherosclerotic plaques, ↓ uptake in the liver (24947229, 28144137) and ↓ inflammation (29885417) | 21835236, 28004910, 29382194, 26295063, 24947229, 28144137, 29885417 |
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| Mouse | rHDL loaded with tracer agent | Can be used to detect atherosclerotic lesions (12007282), Gd-based agent allowed for more effective contrast imaging of atherosclerotic plaques (19378935), the use of oxidized ApoA1 improved the uptake in macrophages significantly (24729189), Fe-O-based contrast agent allows specific imaging of cellular and sub-cellular locations of HDL localization (20926130), P2fA2: Effective imaging of atherosclerotic plaques in MRI (19072768) | 12007282, 19378935, 24729189, 20926130, 19072768 |
||
| Other diseases | Alzheimer's disease | Mouse, SAMP8 | ApoE3-rHDL, ApoJ-rHDL | rHDL passes the blood-brain barrier and accelerates Aβ clearance (24527692), accumulation in the cranial region (29116115) | 24527692, 29116115 |
| Cancer | Mouse and human | rHDL with paclitaxel | ↑ cytotoxicity in cancer cell lines than drug alone, ↑ tolerance in-vivo than drug alone (18176115), No drug leakage or remodeling of rHDL, efficient delivery to tumor (24079327), 30% increase uptake into cancer cells than drug alone (19637935) | 18176115, 24079327, 19637935 |
|
| Mouse and human | rHDL loaded with siRNA | Effective delivery to cancer cells via SR-B1(28717350), VEGF siRNA: ↓ VEGF expression levels, ↓ tumor angiogenesis, ↓ intratumoral microvessels (24875759), Effective co-delivery to cancer cell lines over-expressing SR-B1 (28753317) | 28717350, 24875759, 28753317 |
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| Mouse and human | rHDL loaded with imaging agents | Imaging and monitoring of tumor associated macrophages more efficient than (89)Zr-rHDL imaging agent alone (26112022), rHDL labeled with 99mTc and hydrazinonicotinic acid is an effective new radio-tracer for labeling tumors (30543234), apoE3 rHDL-AuNP results in effective labeling of LDLR overexpressing cancer cell lines (29225464) | 26112022, 30543234, 29225464 |
||
| Mouse and human | rHDL loaded with anti-cancer drugs | PTX-HZ08-rHDL NPs target tumors via SR-B1, ↓ drug leakage, ↑ anti-tumor capacity than drug alone (27343697), Triple-negative breast cancer cells better targeted and less off target effects observed in cardiomyocytes (rHDL with apatinib and valrubicin) (28670138), 100-fold improvement in selective therapeutic efficiency (rHDL with fenretinide) (24459664), ↑ anti-tumor response compared to free drug cocktail, ↑ anti-cancer effects, ↑in-vitro cell toxicity (rHDL with paclitaxel and doxorubicin) (27982602), Effective receptor mediated uptake, overcomes solubility barrier of AD-32 [rHDL with valrubicin (AD-32)] (22393294) | 27343697, 28670138, 24459664, 27982602, 22393294 |
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| Human, clinical trial Phase 1 | rHDL loaded with miRNA (MRX34) | Safe, well-tolerated, preliminary evidence of anti-tumor activity | 27917453 | ||
| Mouse | HDL-NP, gold nanoparticle conjugated | Selectively promotes cholesterol efflux, not cholesterol delivery, to lymphoma cells, resulting in cell starvation and apoptosis | 23345442 |