The genetic and biologic factors that predispose individuals to forming hernias are not well understood. Several smaller series have suggested that ventral and inguinal hernia formation may be due to weakness of the abdominal wall, possibly secondary to defects in collagen deposition and metabolism. Certain studies have shown higher ratios of Type III collagen (immature) to Type I collagen (mature), at both the protein and mRNA level, in patients with abdominal hernias as compared to those without. Furthermore, other reports indicate that these differences in the levels of mature collagen might be due to underlying differences ion the expression of certain matrix metalloproteinase (MMPs), which are largely responsible for collagen remodeling. MMPs -1, -2, -3, -9, and -13 have been shown to be upregulated in connective tissue injury, and alterations in both MMP-2 and fibrillar collagen can interfere with normal wound healing. Furthermore, Bellon et. al. have shown an overexpression of MMP-2 in fibroblasts in patients with direct inguinal hernias, and Zheng's group detected MMP-13 overexpression in tissue samples from patients with recurrent inguinal hernias. So far, no studies have addressed the role of collagen deposition and MMPs in the formation of hiatal and paraesophageal hernias. Preliminary work at our institution has, however, shown a greater than 50% reduction in the elastin content of the phrenoesophageal and gastrohepatic ligaments ("PEL" and "GHL", respectively) of those patients with a hiatal hernia compared to those without herniation. Additionally, the elastic fibers in the PEL and GHL frequently displayed fragmentation and distortion despite the lack of a visible inflammatory response. (J.A. Curci and N.J. Soper, unpublished results) Nevertheless, neither our early work, nor any of the studies from outside institutions have looked at ways of screening patients (i.e. via blood sampling) to detect those at a higher risk for such hernia occurrence. Currently, new MMP-inhibitory drugs are being studied as methods to potentially block or slow the development of other MMP-dependent conditions such as abdominal aortic aneurysm (AAA). Along these lines, if patients with a genetic/biologic predisposition to hernia formation could be readily identified, then this presents a potential point of medical intervention in preventing future hernia development.