Kidney as modulator and target of “good/bad” HDL

Zhong, Jian; Yang, Haichun; Kon, Valentina

doi:10.1007/s00467-018-4104-2

Cited by 16 publications

(19 citation statements)

References 80 publications

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“…[9][10][11][12][13] In the kidneys, both HDL-C deficiency J o u r n a l P r e -p r o o f and HDL-C dysfunction have been linked to vascular atherosclerosis and tubulointerstitial injury in experimental studies. [14][15][16] These possible dual effects of HDL-C are in accordance with the results of epidemiological studies showing a U-shaped association between HDL-C levels and the risk of CKD, CVD or all-cause mortality in various populations. [17][18][19] Although several studies have reported an association of low HDL-C levels with incident CKD, both low and high HDL-C levels were associated with a GFR loss, CKD progression and end-stage kidney disease (ESKD) in a study of nearly 2 million male US veterans.…”

Section: Introductionsupporting

confidence: 86%

“…11 Smaller modified HDL-C particles and HDL components, such as ApoA1, may interact with several renal cell classes, as they are filtered in the glomeruli and reabsorbed in the proximal tubuli. 16 Indeed, oxidized HDL-C enhances the production of reactive oxygen species and upregulates the expression of pro-inflammatory factors in human proximal tubule epithelial cells in a dose-dependent manner. 15 Associations of higher HDL-C levels with the GFR change rate and risk of rapid GFR decline were found in subjects who reported performing little or no physical activity, and the association with the GFR change rate was significant for men and subjects with higher hs-CRP levels only.…”

Section: Discussionmentioning

confidence: 99%

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Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Melsom

Norvik

Enoksen³

et al. 2021

Kidney International Reports

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Section: Introductionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Melsom

Norvik

Enoksen³

et al. 2021

Kidney International Reports

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“…In part, this is due to limitations imposed by the glomerular filtration barrier, which restricts passage of most plasma proteins and large molecules. However, disruption in the glomerular filter that characterizes proteinuric kidney injury predicts increased passage of greater number of particles, including apoAI/HDL(38). Our study in NEP25 + mice shows co-localization of apoAI with podocytes, which suggests passage of this plasma protein across the glomerular filtration barrier.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, kidneys express transporters for apolipoproteins and HDL, including ATP-binding cassette transporter-A1 (ABCA1) and scavenger receptor-BI (SRBI) which we recently found have an important role in binding, trafficking or salvage of filtered apoAI. (38) Deficiency or disruption of the transporters or receptor affects tubular handling of apoAI(39, 40). Thus, increased urinary apoAI in our NEP25 + model likely reflects disruption of the glomerular filtration barrier together with some degree of tubular damage.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein modulation of proteinuric renal injury

Tsuchida

Zhong

Otsuka

et al. 2019

Laboratory Investigation

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High density lipoprotein (HDL) and its main protein, apolipoprotein AI (apoAI), have established benefits in various cells, but whether these cytoprotective effects of HDL pertain in renal cells is unclear. We investigated the in vitro consequences of exposing damaged podocytes to normal apoAI, HDL, apoAI mimetic (L-4F) and in vivo effects of L-4F on kidney and atherosclerotic injury in a podocyte-specific injury model of proteinuria. In vitro , primary mouse podocytes were injured by puromycin aminonucleoside (PAN). Cellular viability, migration, production of reactive oxygen species (ROS), apoptosis and the underlying signaling pathway were assessed. In vivo , we used a proteinuric model, Nphs1-hCD25 transgenic (NEP25 + ) mice, which express human CD25 on podocytes, and podocyte injury can be induced by immunotoxin (LMB2) and generated a proteinuric atherosclerosis model, NEP25 + :apoE−/− mice, by mating apoE-deficient (apoE−/−) mice with NEP25 + mice. Animals received L-4F or control vehicle. Renal function, podocyte injury and atherosclerosis were assessed. PAN reduced podocyte viability, migration and increased ROS production, all significantly lessened by apoAI, HDL and L-4F. L-4F attenuated podocyte apoptosis and diminished PAN-induced inactivation of Janus family protein kinase-2/ signal transducers and activators of transcription 3. In NEP25 + mice, L-4F significantly lessened overall proteinuria, and preserved podocyte expression of synaptopodin and cell density. Proteinuric NEP25 + :apoE−/− mice had more atherosclerosis than non- proteinuric apoE−/− mice and these lesions were significantly decreased by L-4F. Normal human apoAI, HDL and apoAI mimetic protect against podocyte damage. ApoAI mimetic provides in vivo beneficial effects on podocytes that culminate in reduced albuminuria and atherosclerosis. The results suggest supplemental apoAI/apoAI mimetic may be novel candidates to lessen podocyte damage and its complications.

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“…It was reported that HDL function was decreased in CKD patients. HDL components isolated from CKD patients were changed by biochemical and mass spectrometry analyses, which demonstrated that levels of apoAI, apoAII, apoM, paraoxonase were decreased, and levels of serum amyloid A (SAA), apoCII, lipoprotein-associated phospholipase A2 were increased[23]. Our previous work indicated that the decrease of angiopoietin-like protein 3 level might contribute to the reduced capacity of cholesterol efflux in female T2DM patients…”

mentioning

confidence: 98%

Relationship of para- and perirenal fat and high-density lipoprotein and its function in patients with type 2 diabetes mellitus

Ke¹,

Wang²,

Liu³

et al. 2020

Preprint

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Background Para- and perirenal fat is a fat pad surrounding the kidneys. Recent researches have showed the association between para- and perirenal fat and cardiovascular diseases including atherosclerosis, hypertension and so on. Limited studies have explored the relation between para- and perirenal fat and serum high density lipoprotein (HDL) level, but the results were inconsistent. We aimed to assess the relationship between para-perirenal ultrasonographic fat thickness and serum HDL level and cholesterol efflux capacity of HDL in patients with type 2 diabetes mellitus (T2DM). Methods We recruited 58 subjects with T2DM and collected anthropometric indices including height, weight, waist circumference and so on. Para-perirenal ultrasonographic fat thickness (PUFT) was measured via ultrasound. Serum lipid profile and other metabolic indices were determined as well. Then we analyzed the relationship between PUFT and HDL level and cholesterol efflux capacity in all patients and subgroups divided by gender and body mass index (BMI). Results Patients with higher PUFT have lower serum HDL level but increased cholesterol efflux capacity of HDL. Further analysis showed that PUFT negatively correlated with serum HDL level in all patients, with no difference in group divided by BMI. While subgroup analysis divided by gender indicated that the relationship only existed in males. In addition, PUFT was positively correlated with cholesterol efflux capacity in all patients. However, subgroup analysis showed that PUFT did not significantly correlated with cholesterol efflux capacity in males and BMI ≥28kg/m 2 . Multiple stepwise regression analysis showed an independent association of PUFT and serum HDL level and cholesterol efflux capacity. Conclusions PUFT is closely correlated with serum HDL level and cholesterol efflux capacity in patients with T2DM.

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Kidney as modulator and target of “good/bad” HDL

Cited by 16 publications

References 80 publications

Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Lipoprotein modulation of proteinuric renal injury

Relationship of para- and perirenal fat and high-density lipoprotein and its function in patients with type 2 diabetes mellitus

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