High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

Riwanto, Meliana; Landmesser, Ulf

doi:10.1194/jlr.r037762

Cited by 141 publications

(132 citation statements)

References 204 publications

(274 reference statements)

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“…Another limitation is that HDL was obtained from healthy young donors. As HDL functions can be compromised by aging, cardiovascular disease and T2DM (Riwanto and Landmesser, 2013), it will be important in the future to understand how HDL purified from aged cognitively healthy individuals, AD subjects, or patients with cardiovascular risk factors may affect cerebrovascular function and Ab accumulation especially in combination with apoE. It should be noted that the concentration of HDL used in the present study is estimated to be 7-fold lower compared to normolipidomic individuals.…”

Section: Discussionmentioning

confidence: 93%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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Amyloid plaques, consisting of deposited beta-amyloid (Ab), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Ab is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Ab transport across bioengineered human cerebral vessels. These lipoproteins facilitate Ab42 transport more efficiently than Ab40, consistent with Ab40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Ab transport, also consistent with the well-established role of apoE4 in Ab deposition in AD.

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Section: Discussionmentioning

confidence: 93%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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“…These other functions, for example towards endothelial cells, are difficult to be measured in large cohort studies. 4,11,12 Therefore, it is important to unravel the molecular basis of HDL dysfunction. The structural correlates of HDL dysfunction, whether HDL-subclasses, proteins or lipids or modifications thereof, can be much more easily translated into robust high throughput analytical methods than the recording of HDL functionality by cell-based bioassays.…”

Section: Cholesterol Efflux Capacity As a Risk Factor For Cardiovascumentioning

confidence: 99%

“…This micro-heterogeneity is further increased in HDL of patients with various inflammatory diseases, including CHD, by the loss or structural modification of typical HDL constituents or by the acquisition of atypical constituents. 5,11,12 Of note, many physiological as well as pathological components and modifications are present at concentrations which are several orders of magnitude lower than the concentration of HDL-cholesterol or even HDL particles and hence reflected by measurements of neither HDL-cholesterol, nor apoA-I, nor HDLparticle concentrations. 5 In the search for biomarkers that reflect the functionality of HDL 6 better than these high-throughput markers, bioassays have been developed for clinical studies as well as for discovery of functional biomarkers by proteomics and lipidomics.…”

Section: Introductionmentioning

confidence: 99%

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially antiatherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

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“…In particular, conditions associated with both acute and chronic inflammatory processes, such as ischemic vascular events, infections, type 2 diabetes (T2DM), obesity, metabolic syndrome, autoimmune disorders, and chronic kidney disease, have been associated with HDL displaying impaired endothelial protective activities (Riwanto and Landmesser 2013). Indeed, HDL isolated from these patients failed to promote NO production, to exert antioxidant and anti-inflammatory effects, and to favor endothelial integrity in vitro (Riwanto and Landmesser 2013).…”

Section: Effect On Hdl Ability To Preserve Endothelial Cell Homeostasismentioning

confidence: 99%

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

Gomaraschi

Adorni

Banach

et al. 2014

Handbook of Experimental Pharmacology

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High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

Cited by 141 publications

References 204 publications

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

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