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

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Abstract

The strong inverse relationship between low levels of high-density lipoproteins (HDLs) and atherosclerotic cardiovascular disease (CVD) led to the designation of HDL as the “good” cholesterol. The atheroprotection is thought to reflect HDL’s capacity to efflux cholesterol from macrophages, followed by interaction with other lipoproteins in the plasma, processing by the liver and excretion into bile. However, pharmacologic increases in HDL-C levels have not led to expected clinical benefits, giving rise to the concept of dysfunctional HDL, in which increases in serum HDL-C are not beneficial due to lost or altered HDL functions and transition to “bad” HDL. It is now understood that the cholesterol in HDL, measured by HDL-C, is neither a marker nor the mediator of HDL function, including cholesterol efflux capacity. It is also understood that besides cholesterol efflux, HDL functionality encompasses many other potentially beneficial functions, including antioxidant, anti-inflammatory, antithrombotic, anti-apoptotic, and vascular protective effects that may be critical protective pathways for various cells, including those in the kidney parenchyma. This review highlights advances in our understanding of the role kidneys play in HDL metabolism, including the effects on levels, composition, and functionality of HDL particles, particularly the main HDL protein, apolipoprotein AI (apoAI). We suggest that normal apoAI/HDL in the glomerular filtrate provides beneficial effects, including lymphangiogenesis, that promote resorption of renal interstitial fluid and biological particles. In contrast, dysfunctional apoAI/HDL activates detrimental pathways in tubular epithelial cells and lymphatics that lead to interstitial accumulation of fluid and harmful particles that promote progressive kidney damage.

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Authors and Affiliations

  1. Departments of Pediatrics, Vanderbilt University Medical Center, 1161 21st Avenue South, C-4204 Medical Center North, Nashville, TN, 37232-2584, USA

    Jianyong Zhong, Haichun Yang & Valentina Kon

  2. Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Jianyong Zhong & Haichun Yang

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Zhong, J., Yang, H. & Kon, V. Kidney as modulator and target of “good/bad” HDL. Pediatr Nephrol 34, 1683–1695 (2019). https://doi.org/10.1007/s00467-018-4104-2

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