Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structural changes in large arteries are often considered the predominant mechanism responsible for decreased baroreflex sensitivity and baroreceptor resetting in hypertension, atherosclerosis, and aging. Recent work has demonstrated that "functional" mechanisms, both at the level of the peripheral sensory endings and within the central nervous system, contribute significantly to altered baroreflex responses. We have conducted both reductive studies of mechanoelectrical transduction in cultured baroreceptor neurons and integrative studies with in vivo recordings of the activity of baroreceptor afferent fibers and efferent sympathetic nerves. Results suggest that the primary mechanism of mechanical activation of baroreceptor neurons involves opening of stretch-activated ion channels susceptible to blockade by gadolinium. Baroreceptor nerve activity is modulated by the activity of potassium channels and the sodium-potassium pump and by paracrine factors, including prostacyclin, oxygen free radicals, and factors released from aggregating platelets. Endothelial dysfunction and altered release of these paracrine factors contribute significantly to the decreased baroreceptor sensitivity in hypertension and atherosclerosis. The central mediation of the baroreflex depends on the pulse phasic pattern of afferent baroreceptor discharge. Baroreflex-mediated inhibition of sympathetic nerve activity is well maintained during pulse phasic afferent activity. Continuous, nonphasic baroreceptor discharge or a rapid (> 1.5 Hz) pulse phasic discharge results in disinhibition of sympathetic activity. This disinhibition during continuous baroreceptor input is exaggerated with aging. Thus, a defect in central mediation of the baroreflex may be a major cause of the impaired baroreflex and sympathoexcitation in the elderly. In summary, functional neural mechanisms, in addition to structural vascular changes, contribute importantly to altered baroreflex responses in normal and pathophysiological states.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Structural versus functional modulation of the arterial baroreflex. 754 54

Nicotine is a strong activator of the hypothalamus pituitary adrenal (HPA) axis. Smoking of only two cigarettes consistently activates the HPA axis of habitual smokers. However, while being a habitual smoker only induces small changes of basal HPA axis activity, smoking induces an attenuated responsiveness of the HPA axis to psychological stress, but not to injection of corticotropin releasing hormone (CRH) or physiological load. The latter points to alterations at hypothalamic or other central structures. The further consequences of decreased HPA axis responsiveness are discussed. Chronic inflammation of the airways is a common consequence of habitual smoking, and smokers often present with low-grade systemic inflammation, which may be mediated by HPA axis alterations. However, habitual smokers' monocytes are reported to show an increased sensitivity towards the inflammation suppressing effects of cortisol, while on the one hand, inflammation of the airways appears to be relatively resistant towards glucocorticoid treatment. In conclusion, this pattern of attenuated cortisol responses and decreased glucocorticoid sensitivity may be causally related to disinhibition of inflammatory processes and thereby further stimulate adverse health outcomes, such as airway inflammation or atherosclerosis.
 ...
PMID:The hypothalamic-pituitary-adrenal (HPA) axis in habitual smokers. 1632 48

Cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is an acronym that describes an ultra-rare, hereditary, cerebral small vessel disease. The aim is to summarize current knowledge and recent findings concerning phenotype, genotype, pathogenesis, diagnoses, and treatment options of CARASAL. The method used in the study is a systematic literature review. CARASAL is clinically characterized by a wide range of predominantly central nervous system abnormalities. These include migraine, stroke with central facial palsy, facial pain, non-positional vertigo, cognitive dysfunction with impaired concentration and behavioral disinhibition, REM-sleep behavioral disorder, and depression. CARASAL is caused by point mutations in CTSA encoding cathepsin-A. Cathepsin-A is a carboxypeptidase that associates with the lysosomal enzymes b-galactosidase and neuraminidase, promoting their stabilization. In addition, cathepsin-A degradates endothelin-1. CARASAL is a primary microangiopathy with severe atherosclerosis of arterioles and secondary leukoencephalopathy. So far, 19 patients have been reported. The frequency of CARASAL patients will most likely increase in the future, as CARASAL may be more frequently recognized with the increasingly available methods for genetic testing and advanced imaging techniques. The phenotypic and genotypic spectrum of CARASAL needs to be more extensively investigated and animal models for the disease need to be generated. Currently, the outcome cannot be sufficiently assessed, as too few cases have been reported.
 ...
PMID:Update on hereditary, autosomal dominant cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). 3122 22