Microvascular dysfunction

In many chronic inflammatory diseases, angiogenesis can be identified in the inflamed lesions. For example, in rheumatoid arthritis extensive neovascularization is present in the inflamed synovium where it is one of the earliest histopathological findings [36]. Since in RA synoviocytes exhibit characteristics of tumour cells, including somatic mutations in key regulatory genes such as H-ras and the p53 tumour suppressor, RA can be viewed as a multicentric tumour-like mass that invades and destroys its local environment [37]. Concurrent increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. 

Johnson NP, Gould KL. Clinical evaluation of a new concept resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. J Nucl Med 2005 46 1427-1437... 

Rothenbach, P.A., B. Dahl, J.J. Schwartz, G.E. O Keefe, M. Yamamoto, W.M. Lee, J.W. Horton, H.L. Yin, and R.H. Tumage. 2004. Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction. J Appl Physiol. 96 25—31. 

Gibson CM, Morrow DA, Murphy SA, et al. A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia and inflammation among antiplatelet and antithrombotic agents. The PROTECT-TIMI-30 trial. J Am Coll Cardiol 2006 47 2364-2373. 

Kurose, I., Argenbright, LW, Wolf, R, Lianxi, L, and Granger, DN. 1997. Ischemia/reperfusion-induced microvascular dysfunction role of oxidants and lipid mediators. Am J Physiol 111 H2976-H2982. 

Kurose I, Pothoulakis C, LaMont JT, et al. (1994) Clostridium difficile toxin A-induced microvascular dysfunction. Role of histamine. In J. Clin. Invest. 94 1919-1926. 

After having enumerated all the interventions producing cardioprotection it should be pointed out that frequently it is difficult to differentiate between myocardium and endothelium. Ischemic injury affects the endothelium as well.255 Microvascular dysfunction, expressed as slow flow, is of great prognostic value after a myocardial infarction and can be attributed to endothelial dysfunction.256 Moreover, the endothelium produces Hsp70 by itself257 which decreases i.e IL-6 and i-NOS but upgrades e-NOS 258 endothelium itself is a main source of NO.259 It is of interest however that myocardium and endothelium share the same friends and foes.260... 

Cecchi F, Olivotto I, Gistri R, et al. Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. N Engl J Med 2003 349 1027-1035. 

Lush CW, Kvietys PR. Microvascular dysfunction in sepsis. Microcirculation 2000 7 83-101. 

Stokes, K. Y., Cooper, D., Tailor, A., and Granger, D. N., Hypercholesterolemia promotes inflammation and microvascular dysfunction Role of nitric oxide and superoxide. Free Radic. Biol. Med. 33, 1026-1036 (2002). 

Brewington SD, Abbas AA, Dbton SR, Grines CL, O Neill WW. Reproducible microvascular dysfunction with dobuta-mine infusion in Takotsubo cardiomyopathy presenting with ST segment elevation. Catheter Cardiovasc Interv 2006 68(5) 769-74. 

To illustrate the effects of ROS on microvascular function, ischemia-reperfusion (I/R) will be briefly discussed. A prolonged reduction or absence of blood flow (i.e., ischemia) results in a series of biochemical changes within endothelial cells that will initiate a microvascular inflammatory response upon reintroduction of blood flow to the tissue (i.e., reperfusion).Clinical situations involving I/R-induced microvascular dysfunction include organ transplantation, coronary angioplasty, thrombolytic therapy, and cardiopulmonary bypass. ... 

Voisine P Bianchi C, Khan TA, et al. Normalization of coronary microvascular reactivity and improvement in myocardial perfusion by surgical vascular endothelial growth factor therapy combined with oral supplementation of L-arginine in a porcine model of endothelial dysfunction. J Thorac Cardiovasc Surg 2005 129(6) 1414-1420. 

Two-photon microscopy can be utilized to quantify microvascular flow rates within the kidney. Infusion of a nonfilterable intravenous fluorescent dye results in intravascular cells appearing as dark objects. Endothelial cell dysfunction within the microvasculature can be observed and quantified using the infusion of variously sized, differently colored dextrans or proteins. Movement of these molecules out of the microvasculature and accumulation within the interstitial compartment are readily observed during injury or disease. 

Endothelial dysfunction and microvascular injury start at the interphase of the endothelium with the bloodstream. Reperfusion of ischemic vasculature results in production of excessive quantities of vasoconstrictors, oxygen-free radical formation and neutrophil activation and accumulation. Neutrophils and macrophages further increase... 

Sutton TA, Fisher CJ, Molitoris BA. Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int 2002 62 1539-1549. 

Similarly to arterial hypertension, hypothyroidism may induce left ventricular hypertrophy, diastofic and systolic dysfunction, glomerulosclerosis and renal insufficiency, cerebral edema, microvascular disease and dementia. 

Problems within diabetes treatment can usually be divided into two phases, namely (i) acute and short-term treatment of patients and related to well-being and near-perfect physical abilities for professional and leisure activities, most often related to good metabolic control, (ii) On the other hand, the long-term perspective is preventive treatment of complications, both microvascular and vascular complications. Under special situations such as pregnancy, treatment is critical. A number of co-morbid situations are important heart disease (although not always specifically related to diabetes), obesity (an increasingly important problem), and lipid management (very common). Since 1991, we have seen a rapid development in the treatment of one important issue, namely treatment of erectile dysfunction, which is even more important in diabetic than in nondiabetic individuals. 

Plasma A(3 was examined as a potential risk factor for AD and the related process of cerebral amyloid angiopathy (CAA), but was not consistently elevated in these conditions (de Leeuw et. al., 1999). Recent data from the population-based Rotterdam study, however, demonstrated an association between plasma A 3 and microvascular disease in the brain in APOE e4 carriers (Carmelli et al., 1998 Jeerakathil et al., 2004), suggesting that A(1 might be a cause or marker of cerebrovascular dysfunction. 

UUen, A., G. Fauler, E. Bemhart, C. Nusshold, H. Reicher, H. J. Leis, E. Malle, and W. Sattler. 2012. Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial ceU dysfunction in vitro. 53(9) 1770-81. 

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