Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD

Haarhaus, MathiasKarolinska Institutet,Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Klinisk kemi,Karolinska Institute, Sweden (författare)

Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification. This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney. TNALP has a pivotal role in bone calcification. Experimental overexpression of TNALP in the vasculature is sufficient to induce vascular calcification, cardiac hypertrophy and premature death, mimicking the cardiovascular phenotype often found in CKD and T2DM. Intestinal ALP contributes to the gut mucosal defence and intestinal and liver ALPs might contribute to the acute inflammatory response to endogenous or pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases. We also discuss new drugs that target ALP, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralization.

Brandenburg, VincentRWTH University Hospital Aachen, Germany (författare)
Kalantar-Zadeh, KamyarUniversity of Calif Irvine, CA 92868 USA; University of Calif Los Angeles, CA 90502 USA (författare)
Stenvinkel, PeterKarolinska Institutet,Karolinska Institute, Sweden (författare)
Magnusson, PerLinköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Region Östergötland, Klinisk kemi(Swepub:liu)perma28 (författare)
Linköpings universitetInstitutionen för klinisk och experimentell medicin (creator_code:org_t)

Ingår i:Nature Reviews Nephrology: NATURE PUBLISHING GROUP13:7, s. 429-4421759-50611759-507X

Av författaren/redakt...: Haarhaus, Mathia ...; Brandenburg, Vin ...; Kalantar-Zadeh, ...; Stenvinkel, Pete ...; Magnusson, Per

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