In asthma, it's not the drugs but the inflammation that increases cardiovascular risk, damage

03/31/05

First study to show evidence of a direct impact of asthma to cardiovascular complications, independent of drug therapy influences

San Diego (April 3, 2005) - Epidemiological studies show that the incidence of cardiovascular disease (CVD) complications are increased in long standing cases of asthma. Historically, the complications are often attributed to the chronic drug therapy used to treat asthma.

However, researchers in the Department of Physiology, Brody School of Medicine at East Carolina University discovered that the inflammation associated with asthma directly affects the heart's recovery from a heart attack, confirming the growing body of evidence that indicates asthma may directly, and negatively, impact the cardiovascular system.

"The findings are clinically important because they provide the first evidence of a direct contribution of asthmatic conditions to cardiovascular complications, independent of any asthma drug therapy," according to Surovi Hazarika, the lead author. "If the findings are confirmed in human trials, asthma could be identified as a potential risk factor for post-operative complications and recurrent events following such cardiology interventions as angioplasty," she added.

*Paper presentations: Hazarika is presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.

"Airway inflammation increases infarction after myocardial ischemia-reperfusion in mice," 12:30 p.m.-3 p.m. Sunday April 3, Physiology 389.21/board #A713. On view 7:30 a.m. - 4 p.m.

"Neutrophil degranulation and ischemia-induced expression of neutrophil chemotactic molecules are enhanced in a murine model of asthma," 12:30 p.m.-3 p.m. Monday April 4, Physiology 691.4/board #A690. On view 7:30 a.m. - 4 p.m.

Research for both papers was done by Surovi Hazarika, Michael R. Van Scott and Robert M. Lust of the Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina. The studies are part of a collaborative project between the Lust laboratory, which studies acute coronary syndromes, and the Van Scott laboratory, which studies asthma in animal models.

Improved short- and long-term clinical strategies seen for asthma-CVD co-risks

In the short term this should lead to "improved management strategy of acute coronary syndrome patients with clinical history of asthma. And in the longer term, identification of the precise cause of cardiac changes induced by asthma and the appropriate therapeutic targets should provide better, specific alternatives for patients symptomatic for both asthma and cardiovascular disease, or CVD," Hazarika predicted.

Study shows asthma "helps" heart attract damaging inflammatory cells

The results of the studies indicate that "inflammatory responses associated with asthma enhance the ability of the heart to attract inflammatory cells when injured, and that the inflammatory cells that are attracted are more prone to be damaging," Hazarika said. "The end result is increased recruitment of more highly activated neutrophils to the infarct zone during an acute MI, leading to significantly more cardiac tissue damage," she added.

Evidence for a role of inflammation in the development and progression of cardiovascular diseases has been growing rapidly. Studies demonstrate that blood levels of non-specific biomarkers of systemic inflammation such as C-reactive protein (CRP) correlate with increased risk of myocardial events.

Furthermore, in patients with acute coronary syndrome (ACS), serum myeloperoxidase (MPO) levels, another inflammatory biomarker, indicate the risk of subsequent cardiovascular events. Circulating white blood cells, called neutrophils, are an important part of the immune system, and are the predominant source of MPO. Neutrophils have been shown to play a key role in myocardial infarction (MI, or heart attack), as well as in recovery from MI.

Finding the asthma mechanisms that increase cardiac injury

Inflammation also underlies asthma. Asthma is characterized by increased numbers of inflammatory cells at both local (airways) and systemic levels. As in cardiovascular disease, neutrophils play a significant role in the pathology of asthma. Earlier studies from the Van Scott-Lust laboratory showed that infarct size is increased after an acute MI in both rabbit and mouse models of asthma, with enhanced neutrophil accumulation in the damaged region of the heart, often referred to as the "area at risk."

So "the goal of the current study was to investigate the inflammatory mechanisms underlying the asthma-associated increase in cardiac injury following a heart attack," Hazarika explained.

Asthma symptoms were induced in mice, with a sham treated group used as control. Circulating neutrophils were isolated from the peripheral blood and examined for their activation state by measuring stimulated release of the enzyme myeloperoxidase. Neutrophils isolated from asthmatic animals showed an enhanced rate of MPO release compared to those from control animals (substrate consumption rate of 1.52 + 0.3 hg/ sec vs. 0.29 + 0.08 hg/sec; p < 0.05). "The increased MPO release suggests that the neutrophils have been 'primed' to produce a proportionally larger inflammatory response if stimulated," she said. Also, neutrophils from asthmatic animals showed an enhanced expression of PSGL-1 and CD11b, both key molecules involved in the movement of neutrophils out of blood vessels.

In addition, after experimental induction of myocardial ischemia-reperfusion, the myocardial tissue level of macrophage inhibitory protein-2 (MIP-2), and expression of endothelial P-selectin were higher in asthmatic animals compared to the controls. Both MIP-2 and P-selectin participate in attracting neutrophils out of circulation to the injured tissue, leading to significantly more cardiac tissue damage in asthmatic conditions.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
    Published on PsychCentral.com. All rights reserved.

 

 

Great things are not done by impulse, but by a series of small things brought together.
-- Vincent Van Gogh
 
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