Whereas B+/C+ Tenascin-C and MMP-9 alterations reflect the switch of extra-valvular cardiac damage from left ventricular to left atrial involvement, TIMP-1, ED-A+ Fn, ET-1 and NGAL reflect the further transition from left heart involvement to pulmonary hypertension and consecutive right heart dysfunction. The gene discussed is TNC; the disease is pulmonary hypertension.