Glycosylated CD147 reduces myocardial collagen cross‐linking in cardiac hypertrophy

The mechanism of transition from chronic pressure overload‐induced cardiac hypertrophy to heart failure is still unclear. Angiotensin II (Ang II) may be an important factor that mediates the transition in the end‐stage of cardiac hypertrophy. In the present study, Goldblatt two‐kidney one‐clip (2K1C) rat model was used to simulate Ang II‐induced hypertension. The elevated Ang II not only induced the concentric hypertrophy of left ventricle and cardiac fibrosis, but also increased the expression and glycosylation of CD147 in 2K1C rats. The left ventricular structure and function detected by echocardiogram showed a sign of the transition from cardiac hypertrophy to heart failure in 16 weeks of 2K1C rats. Ang II can activate N‐acetylglucosamine transferase V (GnT‐V), a key enzyme for CD147 glycosylation. Retinoic acid, an agonist of GnT‐V, further increased glycosylated CD147, and activated matrix metalloproteinase‐2/‐9 (MMP‐2 and MMP‐9) in the hypertrophied left ventricle of 2K1C rat. Meanwhile, collagen cross‐linking in the hypertrophied left ventricle significantly reduced in 2K1C rats. On the contrary, tunicamycin, an inhibitor of N‐glycan biosynthesis, inhibited glycosylation of CD147 and activity of MMP‐2 and MMP‐9, and then maintained a stable of collagen cross‐linking in the 2K1C rat hearts. The above results suggested that Ang II increased glycosylated CD147 which activated MMP‐2 and MMP‐9. Collagens were degraded by the activated MMPs and then reduced collagen cross‐linking. Finally, the hypertrophied left ventricle was progressively dilated in chronic pressure overload due to losing the limitation of collagen cross‐linking. Therefore, the compensated hypertrophy of left ventricle gradually transited to congestive heart failure.