High Plasma Levels of Fortilin in Patients with Coronary Artery Disease

Masayuki Aoyama; Yoshimi Kishimoto; Emi Saita; Reiko Ohmori; Kojiro Tanimoto; Masato Nakamura; Kazuo Kondo; Yukihiko Momiyama

doi:10.3390/ijms23168923

High Plasma Levels of Fortilin in Patients with Coronary Artery Disease

Int J Mol Sci. 2022 Aug 10;23(16):8923. doi: 10.3390/ijms23168923.

Authors

Masayuki Aoyama^{1

2}, Yoshimi Kishimoto³, Emi Saita⁴, Reiko Ohmori⁵, Kojiro Tanimoto¹, Masato Nakamura², Kazuo Kondo⁶, Yukihiko Momiyama¹

Affiliations

¹ Department of Cardiology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
² Toho University Graduate School of Medicine, 2-22-36 Ohashi, Meguro-ku, Tokyo 153-8515, Japan.
³ Department of Food Science and Human Nutrition, Faculty of Agriculture, Setsunan University, 45-1 Nagaotouge-cho, Hirakata, Osaka 573-0101, Japan.
⁴ Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
⁵ Faculty of Regional Design, Utsunomiya University, 350 Minecho, Tochigi 321-8505, Japan.
⁶ Faculty of Human Life and Environmental Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.

Abstract

Excessive apoptosis is known to be a common feature of atherosclerotic lesions. Fortilin is recognized to have potent antiapoptotic properties. An increased fortilin expression was demonstrated in atherosclerotic lesions, and fortilin knockout mice developed less atherosclerosis. However, no study has reported blood fortilin levels in patients with coronary artery disease (CAD). We investigated plasma fortilin levels in 384 patients undergoing coronary angiography. CAD severity was evaluated as the numbers of stenotic vessels and segments. CAD was found in 208 patients (one-vessel (1VD), n = 86; two-vessel (2VD), n = 68; and three-vessel disease (3VD), n = 54). Plasma C-reactive protein (CRP) levels were higher in patients with CAD than without CAD (median 0.60 vs. 0.45 mg/L, p < 0.01). Notably, fortilin levels were higher in patients with CAD than without CAD (75.1 vs. 69.7 pg/mL, p < 0.02). A stepwise increase in fortilin was found according to the number of stenotic vessels: 69.7 in CAD(−), 71.1 in 1VD, 75.7 in 2VD, and 84.7 pg/mL in 3VD (p < 0.01). Fortilin levels also correlated with the number of stenotic segments (r = 0.16) and CRP levels (r = 0.24) (p < 0.01). In a multivariate analysis, fortilin levels were independently associated with 3VD. The odds ratio for 3VD was 1.93 (95%CI = 1.01−3.71) for a high fortilin level (>70.0 pg/mL). Thus, plasma fortilin levels in patients with CAD, especially those with 3VD, were found to be high and to be associated with the severity of CAD.

Keywords: apoptosis; atherosclerosis; biomarkers; coronary artery disease; fortilin.

MeSH terms

Animals
Atherosclerosis*
Biomarkers
Coronary Angiography
Coronary Artery Disease*
Mice
Multivariate Analysis
Odds Ratio
Severity of Illness Index

Substances

Biomarkers

Grants and funding

Our study had support in the form of a grant from the Tanuma Green House Foundation. It was also financially supported by Bayer Yakuhin Ltd., Daiichi Sankyo Co., and Pfizer Inc.; however, they played no role in the study design, data analysis, or manuscript preparation.