Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Abstract

Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary L-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+L-lysinezHCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. L-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary L-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of L-lysine. Dietary L-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/ phosphate solution. In conclusion, dietary supplementation of L-lysine ameliorated VC by modifying key pathways that exacerbate VC.

A paradigm shift for bone quality in dentistry: A literature review

“…The degree of bone regeneration [21,87] and the pathological conditions of diseased bone including some types of osteoporosis [88][89][90], osteoarthritis [91], osteopetrosis [92], and cancer metastasis [83,84] were reported to be assessed using the degree of BAp orientation. For example, in the primary type osteoporosis induced by estrogen deficiency, the degree of BAp c-axis orientation both in the cortical and trabecular bone of lumber vertebrae increases along the craniocaudal axis in which principal stress is applied [88].…”

The Role of Vascular Calcification in Heart Failure and Cognitive Decline

“…Dietary L-lysine, vitamin E, and iron effectively reduce vascular calcification in animal models [53,54]. …”

Klotho upregulation by rapamycin protects against vascular disease in CKD

“…In fact, we have already reported that alanine and proline inhibit apoptosis of cultured VSMCs, and that L-lysine supplementation almost completely ameliorated vascular calcification in vivo. 3 Phosphate-induced vascular calcification, especially in the uremic milieu, is thought to involve chondrogenic/ osteogenic transdifferentiation of VSMCs. This type of vascular calcification corresponds morphologically to medial calcification.…”

“…Recently, the attention of several investigators has been drawn to control subclinical chronic inflammation (microinflammation) in the kidney, which probably plays a critical role in promoting progression of diabetic nephropathy. 1,2 In this regard, Awad et al 3 (this issue) report effectiveness of anti-tumor necrosis factor-α (anti-TNF-α) antibody in the amelioration of experimental diabetic nephropathy in Ins2 Akita diabetic mice. Likewise, they observed protection from streptozotocin-induced hyperglycemic renal injury in another mouse model deficient in macrophage-specific TNF-α (CD11b Cre /TNF-α Flox/Flox ).…”