Matrix metalloproteinases and coronary artery disease: a novel therapeutic target.

Matrix metalloproteinases (MMP) are a family of enzymes that selectively digest individual components of the extracellular matrix. Their function has been studied in both normal physiologic processes and pathologic states. In the blood vessel, MMPs play an important role in maintaining the vessel's integrity by breaking down extracellular matrix while new matrix is being synthesized. This is necessary to avoid weakening from continuous mechanical stresses. However, in certain environments, these MMPs may contribute to cardiovascular pathologic processes. The purpose of this review is to first discuss the role of MMPs in coronary vascular disease. Evidence suggests that MMPs contribute to the development of de novo atherosclerotic plaques and postangioplasty restenotic plaques by allowing smooth muscle cells to migrate from the vascular media to the intima. Evidence also suggests that MMPs contribute to the rupture of these plaques by degrading the fibrous cap that surrounds them. With this increased molecular information that concerns the pathogenesis of coronary vascular disease, new molecular therapies aimed at altering these processes are being investigated. The rationale, mode of delivery, and prospects for success of these therapies will also be discussed here.

Intraneuronal convergence of tactile and hormonal stimuli associated with female reproduction in rats.

Stimulation of the vagina and cervix, by mating or manual probing, elicits many behavioral and endocrine changes associated with female reproduction in rats. We and others have identified neurons in the medial preoptic area, medial division of the bed nucleus of the stria terminalis, posterodorsal portion of the medial amygdala, ventromedial hypothalamus, dorsomedial hypothalamus and midbrain central gray that increase Fos expression in response to vaginal-cervical stimulation (VCS). In the present study, we used a double-label immunofluorescent technique to determine if any of these VCS-responsive neurons also contained estrogen receptor-immunoreactivity. We found that over 80% of the VCS-induced Fos-IR neurons in the medial division of the bed nucleus of the stria terminalis also contained estrogen receptor-immunoreactivity. Furthermore, high percentages of VCS-responsive neurons in the medial preoptic area, posterodorsal medial amygdala, ventromedial hypothalamus and midbrain central gray contained estrogen receptor-immunoreactivity as well. These results suggest that sensory and hormonal information associated with female reproduction converge on specific populations of neurons and may be integrated at the molecular level within these neurons.