It has been proposed that COX-2 selectivity could cause imbalance of prostaglandins in the vasculature.  If this were the explanation for the increased cardiovascular risk then low-dose aspirin should negate this effect, which was not the case in the APPROVe trial. Also, the non-selective COX inhibitors, have also shown increase in cardiovascular events.
Another possible explanation was studied by Li H. et al. (2008). They showed that in spontaneously hypertensive rats (SHR) non-selective NSAIDs and the coxibs produce oxidative stress, indicated by enhanced vascular superoxide(O) content and elevated peroxide in plasma, which is in tune with enhanced expression of NADPH oxidase, which was noticed with use of diclofenac and naproxen and, to a lesser degree, rofecoxib and celecoxib. Nitrite in plasma was also decreased suggesting a diminished synthesis of vascular nitric oxide (NO). This decrease in NO synthesis did not result from decreased expression of endothelial nitric oxide synthase (eNOS) because expression of eNOS mRNA was not reduced, and even upregulated for some products. The decrease in NO synthesis could, rather, be explained by loss of eNOS function. For eNOS to be normally functional, it needs to form a dimer and to have its cofactor BH, which is one of the most potent naturally occurring reducing agents. BH is sensitive to oxidation by peroxynitrite (ONOO), which is produced when NO reacts with O, so it has been hypothesized that depletion of BH can occur with excessive oxidative stress (that can be caused by NSAIDs) and, hence, be the cause of eNOS dysfunction. This dysfunction, which is referred to as eNOS uncoupling, causes the production of O by eNOS, thereby leading to more oxidative stress produced by eNOS. In a study, both the selective COX-2 inhibitors and the non-selective NSAIDs produced oxidative stress, with greater effects seen with non-selective NSAIDs use. This could fit with the hypothesis concerning the prostacyclin/thromboxane imbalance. That is, although the non-selective NSAIDs produce more oxidative stress, they prevent platelet aggregation, whereas the COX-2 inhibitors reduce prostacyclin production, and, hence, the cardiovascular risk for the non-selective NSAIDs is not higher than for the coxibs.
Among other hypotheses are increased blood pressure, decreased production of epi-lipoxins (which have anti-inflammatory effects), and inhibition of vascular remodeling when using selective COX-2 inhibitors.