Table 1.

Major milestones in MMP research

Milestone	Investigators
Enzyme degradation of collagen described	Woessner (165)
First MMP described	Gross and Lapiere (60)
MMP-1 purified	Nagai et al. (106)
MMP-2 and -3 identified, isolated, and sequenced	Chin et al. (29), Collier et al. (31), Galloway et al. (55), Okada et al. (109), and Woessner and Nagase (166)
MMP-3 as activator of pro-MMP-1	Murphy et al. (105)
MMP term coined	Okada et al. (110)
TIMP-1 and RECK identified as natural MMP inhibitors	Bauer et al. (10), Oh et al (107), and Sellers et al. (132)
MMP zymogen and mechanism of activation	Chen et al. (27), Milla et al. (104), Rosenblum et al. (123), and Springman et al. (141), among numerous research groups
Crystal structure of collagenase catalytic domain solved	Lovejoy et al. (97)
MMP-7 is the first MMP null mouse generated	Wilson et al. (164)
MMP diversity and expression in human heart failure	Dixon and Spinale (42) and Spinale (138, 139)
MMP diversity and expression in atheromatous plaque	Libby et al. (91)
Plaque rupture and inflammation	Galis et al. (54)
MMP roles in inflammatory and fibrotic responses to myocardial infarction	Lindsey and Zamilpa (95)
MMP imaging in vivo	Zhang et al. (174)

The first 10 milestones are general matrix metalloproteinase (MMP) milestones, while the last 5 relate to MMPs in cardiovascular pathophysiology. TIMP, tissue inhibitor of MMP; RECK, reversion-inducing cysteine-rich protein with kazal motifs.