TABLE 1.
Cardiovascular pathomechanisms of hyperphosphatemia.
| CVD | Underlying mechanisms |
| Hypertension | • Activation of SNS (Mizuno et al., 2016) |
| • Increasing renin expression leading to increased circulating angiotensin levels (Bozic et al., 2014) | |
| • Acute impairment of endothelium-dependent vasodilation (Six et al., 2014) | |
| • Increase endothelin-1 production via up-regulation of aortic endothelin converting enzyme-1 expression (Olmos et al., 2017) | |
| • Down-regulating α-klotho expression in the kidney (Hu et al., 2015) | |
| • Deterioration in renal function (Da et al., 2015; Yoon et al., 2017) | |
| Vascular calcification | • Up-regulate the expression of pit (Shobeiri et al., 2014) |
| • Up-regulate osteogenic transcription of VSMCs (Singh et al., 2019; Voelkl et al., 2019; Bao et al., 2020; Chang et al., 2020; Takashi and Fukumoto, 2020b) | |
| • Pro-inflammatory cytokines (Voelkl et al., 2019; Alesutan et al., 2020) | |
| • Apoptosis and autophagy (Shroff et al., 2008; Liu et al., 2017; Ciceri et al., 2019; Voelkl et al., 2019) | |
| • Reduction of fetuin-A (Voelkl et al., 2019) | |
| • Remodeling of extracellular matrix (Voelkl et al., 2019) | |
| • Oxidative stress (Voelkl et al., 2019) | |
| •α-klotho deficiency (Singh et al., 2019) | |
| Cardiac valve calcification | • Activation of NF-κB-AKT/ERK pathway (Li et al., 2017; Shuvy et al., 2019; Zhou et al., 2020) |
| • Increased expression of pit-1 (Husseini et al., 2013) | |
| Atherosclerosis | • Reduction of eNOS and promotes ROS in endothelial (Stevens et al., 2017; Roumeliotis et al., 2020) |
| • Increase of FGF-23 and α-klotho deficiency (Hu and Moe, 2012; Mencke et al., 2015; Richter et al., 2016; Verkaik et al., 2018) | |
| • Endothelial cell apoptosis (Roumeliotis et al., 2020) | |
| • FGF-23 related dyslipidemia (Ellam and Chico, 2012) | |
| • Reduction of calcitriol promoting ox-LDL uptake in macrophages (Oh et al., 2009) | |
| LVH and VF | •α-klotho independent binding of FGF-23 with FGFR4 (Faul et al., 2011; Grabner et al., 2015; Leifheit-Nestler et al., 2016) |
| • Ca2+ dependent cardiomyocyte hypertrophy (Ca2+-CAMK II- IP3 pathway) (Mhatre et al., 2018) | |
| • FGF-23 induced ROS and RAAS (Böckmann et al., 2019; Dong et al., 2019) |