Article

Microvascular responses to cardiovascular risk factors.

Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Microcirculation (New York, N.Y.: 1994) (Impact Factor: 2.26). 04/2010; 17(3):192-205. DOI: 10.1111/j.1549-8719.2009.00015.x
Source: PubMed

ABSTRACT Hypertension, hypercholesterolemia, diabetes, and obesity are among a growing list of conditions that have been designated as major risk factors for cardiovascular disease (CVD). While CVD risk factors are well known to enhance the development of atherosclerotic lesions in large arteries, there is also evidence that the structure and function of microscopic blood vessels can be profoundly altered by these conditions. The diverse responses of the microvasculature to CVD risk factors include oxidative stress, enhanced leukocyte- and platelet-endothelial cell adhesion, impaired endothelial barrier function, altered capillary proliferation, enhanced thrombosis, and vasomotor dysfunction. Emerging evidence indicates that a low-grade systemic inflammatory response that results from risk factor-induced cell activation and cell-cell interactions may underlie the phenotypic changes induced by risk factor exposure. A consequence of the altered microvascular phenotype and systemic inflammatory response is an enhanced vulnerability of tissues to the deleterious effects of secondary oxidative and inflammatory stresses, such as ischemia and reperfusion. Future efforts to develop therapies that prevent the harmful effects of risk factor-induced inflammation should focus on the microcirculation.

1 Follower
 · 
86 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects. Copyright © 2015 the authors 0270-6474/15/353851-15$15.00/0.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess whether epicardial and microvascular coronary artery spasm in response to acetylcholine (ACH) is associated with markers of inflammation, platelet stimulation, and endothelial activation in patients with angina and unobstructed coronary arteries. Patients with angina pectoris despite angiographically normal coronary arteries represent a diagnostic and therapeutic challenge. Both impaired coronary microvascular dilatory responses as well as diffuse distal epicardial and microvascular coronary artery spasm have been described as possible pathogenic mechanisms. Although inflammation has been proposed to play a pathogenic role in angina, an association between ACH-induced coronary vasospasm and inflammation in Caucasians has not been reported previously in this context. We assessed 62 consecutive patients (26 men, age 60±10 years) with chest pain despite angiographically unobstructed coronary arteries (<50% stenosis) who underwent intracoronary ACH testing for the diagnosis of coronary artery spasm. High-sensitivity C-reactive protein (hs-CRP), e-selectin, neopterin, and sCD40L concentrations were measured in all patients before ACH testing. The ACH test was considered to be 'positive' in the presence of (a) angina and at least 75% coronary diameter reduction (epicardial coronary artery spasm) or (b) ischemic ST-shifts and angina in the absence of epicardial spasm (microvascular spasm). Eight patients without angina pectoris served as a control group. The ACH test was positive in 48 patients (77%). Twenty-seven patients had epicardial spasm (56%) and 21 patients had microvascular spasm (44%). Epicardial spasm was diffuse in 26 patients (96%) and focal in one patient (4%). Elevated hs-CRP, e-selectin, and sCD40 ligand concentrations were significantly (P≤0.05) associated with a positive ACH-test response. Hs-CRP (odds ratio 1.54, confidence interval 1.02-2.33, P=0.04) and sCD40 ligand (odds ratio 1.001, confidence interval 1.00-1.001, P=0.003) were predictors for a positive ACH test on multivariate analysis. None of the patients in the control group developed epicardial or microvascular spasm during ACH testing. Epicardial and microvascular coronary spasm in response to ACH correlate significantly with hs-CRP and sCD40 ligand concentrations in patients with angina pectoris and angiographically unobstructed coronary arteries. These results suggest that an association exists between inflammation and coronary artery spasm in patients with angina pectoris despite unobstructed coronary arteries and studies are needed to explore the mechanisms underlying this association.
    Coronary Artery Disease 11/2014; 26(2). DOI:10.1097/MCA.0000000000000181 · 1.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review.
    Frontiers in Cellular Neuroscience 03/2015; 9. DOI:10.3389/fncel.2015.00018 · 4.18 Impact Factor

Full-text (2 Sources)

Download
46 Downloads
Available from
May 20, 2014

Similar Publications