What is the pathophysiology of cyclooxygenase (COX) deficiency?

Updated: Feb 19, 2019
  • Author: George T Griffing, MD; Chief Editor: George T Griffing, MD  more...
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Answer

Two types of platelet COX-1 deficiency have been recognized. The type 1 defect is characterized by a complete absence of COX-1 protein in platelets. In the type 2 deficiency, on the other hand, a normal level of protein exists, but COX-1 enzymatic activity is impaired. The physiologic consequences of COX deficiency, however, are best described as acquired, rather than inherited, disorders.

The effect of COX-1 deficiency varies from tissue to tissue and largely is determined by the fate of the end products. Several studies have concluded that direct inhibition of COX-1 coincides with a loss of cytoprotection. In turn, COX-1 deficiency has been deemed as a significant participant in gastric and renal pathology. [5]

However, Langenbach and colleagues reported that mice deficient in COX-1 live uneventful lives despite a 99% reduction in overall prostaglandin production. [6] He also emphasized that a lack of gastric and renal pathology existed in spite of observed prostaglandin deficiency. Confirming earlier literature, Langenbach reported that female mice deficient in COX-1 had difficulties with parturition, while male mice deficient in COX-1 were unimpaired. Langenbach also has demonstrated that, contrary to popular belief, COX-1 deficiency correlates with reduced edema in the face of inflammatory mediators that increase arachidonate, illuminating its significance in the inflammatory cascade.

Without significant controversy, the consensus has been that the inhibition of COX-2 is responsible, in part, for the antipyretic, analgesic, and anti-inflammatory properties of NSAIDs. However, novel investigations using genetically altered COX knockout mice have uncovered new ramifications associated with COX-2. First, Lim and colleagues observed that COX-2–deficient female mice incurred reproductive failures via abnormalities of ovulation, fertilization, implantation, and decidualization, although follicular development was normal. [7]

Independently, Dinchuck and coauthors described reduced neonatal viability in mice deficient in COX-2, as a consequence of renal dysplasia, cardiac fibrosis, infertility, and endotoxin-induced, hepatocellular cytotoxicity. [8] He concluded that COX-2 deficiency does not affect viability in utero and that heterozygous and wild-type mice do not have disease. Cheng and colleagues subsequently cited the importance of COX-2 as a "mediator of increased renin production in response to inhibition of angiotensin II production." [9] As a result, they proposed that a component of the renin-angiotensin feedback system may be modulated by COX-2 expression.

Through the evolving study of COX, new theories have been integrated into previously well-described pathways. Nevertheless, the influence that COX has on each cell, tissue, organ, and system results from precursor, product, and receptor variability.


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