High molecular weight adiponectin inhibits vascular calcification in renal allograft recipients

<div><p>Background</p><p>Adiponectin (ADPN) prevents the development/recurrence of cardiovascular events via its anti-atherogenic effects. However, few long-term studies have examined the changes in serum ADPN levels and arterial calcification seen in renal allograft recipients.</p><p>Subjects and methods</p><p>The effects of the serum ADPN level on arterial calcification were examined in 51 Japanese renal allograft recipients. Abdominal aorta calcification was evaluated on computed tomography using the aortic calcification area index (ACAI). The change in the ACAI and serum high-molecular-weight (HMW)—ADPN fractions were studied over an 8-year period. The arterial expression of ADPN, ADPN receptors (AdipoR)1 and 2, and T-cadherin (cadherin-13) were also examined by immunohistochemistry.</p><p>Results</p><p></p><p></p><p>The change in the ACAI were grouped into quartiles and compared with the alterations in the serum levels of each ADPN fraction over an 8-year period. The change in the ACAI was much lower in the patients with highly elevated HMW-ADPN levels.</p><p></p><p></p><p>Multiple regression analysis demonstrated that an advanced age at transplant and a history of cardiovascular complications were associated with an increased change in the ACAI, while higher HMW-ADPN concentrations were associated with improvements in the ACAI. Serum HDL-C level was also identified as a positive factor to increase serum HMW-ADPN level.</p><p></p><p></p><p>In immunohistochemical examinations, ADPN was detected on CD31-positive arterial endothelial cells from renal allograft biopsy samples. ADPN co-localized with T-cadherin and AdipoR1, but only partially co-localized with AdipoR2.</p><p></p><p></p><p>Conclusion</p><p>Both HMW-ADPN and HDL-C might inhibit the progression of vascular calcification by promoting ADPN binding to vascular endothelial cells via T-cadherin and AdipoR in Japanese renal allograft recipients.</p></div

The subjects’ baseline characteristics.

<p>The subjects’ baseline characteristics.</p

ADPN, AdipoR1/R2 and cadherin-13 (T-cadherin) expression in renal allografts.

<p>ADPN and AdipoR1 co-localized on the arterial endothelium (arrow) in cases 1 [2A] and 2 [2B]. The endothelium exhibited weaker AdipoR2 expression (arrow) than AdipoR1 expression in cases 1 [2C] and 2 [2D]. ADPN and cadherin-13 co-localized linearly on vascular endothelial cells (arrow) in cases 1 [2E] and 2 [2F].</p

The influence of the serum HMW-ADPN level on the change in the ACAI in renal allograft recipients.

<p>The annual change in the ACAI was divided into 4 quartiles (Q1, <0.006, n = 13; Q2, 0.006–0.172, n = 12; Q3, 0.172–0.413, n = 13; Q4, >0.413, n = 13). The annual changes in both the absolute [1A] and relative [1B] serum HMW-ADPN levels became smaller as abdominal aortic calcification (ACAI) progressed (p<0.01, according to Dunn’s test). The annual change in the serum non-HMW-ADPN level [1C] also tended to decline as the ACAI increased. On the contrary, the annual change in the relative serum non-HMW-ADPN level [1D] significantly increased as the ACAI rose (p<0.05, according to Dunn’s test).</p

The factors that influenced the changes in the ACAI in renal allograft recipients.

<p>The factors that influenced the changes in the ACAI in renal allograft recipients.</p

The influenced factor on post transplant DM in renal transplant subjects.

<p>The influenced factor on post transplant DM in renal transplant subjects.</p

Characteristics of study subjects in transplants.

<p>Characteristics of study subjects in transplants.</p

The association of visceral fat area and serum adiponectin value between CVD and non-CVD patients.

<p>Visceral fat area were higher in CVD patients [A]. There were no significant difference in subcutaneous fat area between two groups [B]. HMW ADPN levels and HMW adiponectin ratio were lower in CVD patients [C] and [D]. LMW ADPN ratio was higher in CVD patients [F]. There was no significant difference in LMW ADPN level between two groups [E].</p

Factors influenced of factor on HMW ADPN and HMW ADPN ratio in renal transplant subjects.

<p>Factors influenced of factor on HMW ADPN and HMW ADPN ratio in renal transplant subjects.</p

The influenced factor on cardiovascular disease in renal transplant subjects.

<p>The influenced factor on cardiovascular disease in renal transplant subjects.</p