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Importantly, there were no cardiovascular adverse events, no clinically significant changes in blood pressure or heart rate, no alterations in thyroid function, no immunogenicity with no anti-AOD-9604 antibodies detected, and no signs of tolerance or receptor desensitization

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In wild-type mice, occludin mRNA shows clear circadian oscillation, which is lost in rhythm-disrupted mice and accompanied by impaired barrier integrity (68)

VSMC senescence induced by Ang II is another important aspect of VSMC dysfunction