P-517: Plasma tissue inhibitor of metalloproteinase-1 and pro-collagen III N peptide are elevated in left ventricular hypertrophy

Essential hypertension (EH) aortic stenosis (AS) and hypertrophic obstructive cardiomyopathy (HOCM) can cause left ventricular hypertrophy (LVH). LVH is associated with increased collagen concentrations in the heart but the mechanisms causing LVH in EH, AS and HOCM are different. Collagen synthesis (fibrogenesis) can be monitored by measurement of pro-collagen III N peptide (PIIINP) which measures synthesis of mature collagen III. Inhibition of degradation was assessed by plasma tissue inhibitor of metalloproteinase -1 (TIMP-1) which inhibits the activity of metalloproteinases. We investigated levels of TIMP-1 and PIIINP in patients with the three types of LVH. Patients with EH had never been treated or had been off treatment for one month and patients with AS had blood samples taken preoperatively for PIIINP and TIMP-1. The results for the EH, AS and HOCM groups were compared with seventeen normotensive controls. Heparinised plasma was used in the assays for TIMP-1 and PIIINP which were measured by ELISA and RIA respectively. (See <cross-ref type="tbl" refid="tb1">Table</cross-ref>) <tbl id="tb1" loc="float"><tblbdy top-stubs="1"><r><c cspan="1" rspan="1">LVH</c><c cspan="1" rspan="1">No patients</c><c cspan="1" rspan="1">Median PIIINP U/ml 95% limits</c><c cspan="1" rspan="1">Median TIMP-1 ng/ml 95%limits</c></r><r><c cspan="1" rspan="1">Control</c><c cspan="1" rspan="1">17</c><c cspan="1" rspan="1">0.53 (0.34-0.70)</c><c cspan="1" rspan="1">178 (99-330)</c></r><r><c cspan="1" rspan="1">EH</c><c cspan="1" rspan="1">31</c><c cspan="1" rspan="1">0.59 (0.33-0.78)</c><c cspan="1" rspan="1">380 (161-1356)<cross-ref type="fn" refid="tb1-fn1">*</cross-ref></c></r><r><c cspan="1" rspan="1">AS</c><c cspan="1" rspan="1">27</c><c cspan="1" rspan="1">0.78 (0.53-1.32)<cross-ref type="fn" refid="tb1-fn1">*</cross-ref></c><c cspan="1" rspan="1">270 (132-648)</c></r><r><c cspan="1" rspan="1">HCOM</c><c cspan="1" rspan="1">12</c><c cspan="1" rspan="1">0.72 (0.58-0.89)<cross-ref type="fn" refid="tb1-fn1">*</cross-ref></c><c cspan="1" rspan="1">258 (160-351)</c></r></tblbdy><tblfn id="tb1-fn1"><no>*</no> p<0.05 in comparison to controls</it> </tblfn></tbl> Elevated levels of collagen in the left ventricule in EH arise from both increased collagen synthesis as well as decreased collagen degradation whereas in AO and HOCM the increased heart collagen is associated with increased collagen III synthesis. This suggests that LVH can arise by different biochemical mechanisms.