The Connection between Inflammation and Cardiovascular Disease

//The Connection between Inflammation and Cardiovascular Disease

The Connection between Inflammation and Cardiovascular Disease

by Mark Johnson, M.S. Senior Director of Surgery

Heart disease is a major cause of morbidity and mortality, particularly in developed nations. Classically, cardiovascular disease (CVD) was thought to be a buildup of fat on the arterial wall that eventually blocks blood flow, leading to a heart attack or stroke. However, the process also involves inflammatory responses that impact the endothelial cell lining of the arteries. The source of this inflammation includes infectious agents, e.g., herpes viruses and Chlamydia pneumonia, as well as smoking, hyperglycemia, oxidized low-density lipoprotein (LDL), and sheer stress on the vessel wall as a result of hypertension.

Genetic factors may also play a role in the magnitude and duration of the inflammatory response. These inflammatory stimuli cause endothelial cells to activate the immune system to deal with the problem, including release of the transcription factor, NF-kB, which promotes production of the early cytokines such as TNF-α and IL-6, chemokines such as MCP-1, and adhesion molecules. The chemokines attract monocytes and T lymphocytes (T cells) from the blood stream, allowing monocytes to travel across the endothelial barrier and become macrophages. Entry of monocytes into the vessel wall is a key factor in the development of atherosclerosis, as blocking monocyte migration has ameliorated atherosclerosis in in vivo models (ref). Once inside the intima, these mononuclear cells produce proinflammatory cytokines such as IL-1, IL-6, and TNF-α to stimulate the inflammatory cascade. Metalloproteinases are also released, promoting smooth muscle cell proliferation and uptake of LDL by these macrophages to form foam cells.

LDL uptake can lead to deposition of a fatty streak that can form a necrotic plaque covered with a fibrous cap produced by a balance between collagen deposition and degradation. Further inflammation can thin and potentially rupture the cap, exposing thrombotic substances to the blood, leading to local thrombus formation and downstream micro embolization (ref). Furthermore, inflammatory cytokines activate platelets expressing P-selectin and CD40, thus increasing platelet-platelet adhesiveness (ref). Cytokines also signal the production of acute phase proteins, such as fibrinogen serum amyloid A and C-reactive proteins, which have been used as biomarkers to assess cardiovascular risk in patients. In addition, both T and B lymphocytes, macrophages, and dendritic cells reside in the arterial wall (lamina adventitia) of non-inflamed aortas, suggesting that the adaptive immune response, and particularly lymphocytes, is also involved in CVD.

Therapeutic strategies for CVD aim to prevent the development or limit progression of the disease. Perhaps the largest breakthrough in this field was the development of statins (atorvastatin and simvastatin, among others) (refs) for treating high cholesterol levels and reducing cardiovascular risk in patients. Interestingly, statins may slow progression of disease at a rate and to an extent that cannot be attributed to lower LDL alone, putatively due to changing endothelial-dependent nitric oxide bioavailability, inhibition of oxidative stress, and anti-inflammatory activity. Therefore, these drugs may impact the biology of the plaque and slow down disease progression via modulating inflammatory responses. Future work should explore the connection between inflammation and CVD to help develop more effective therapies.

By |2017-07-04T10:27:23+00:00February 18th, 2015|Blog|Comments Off on The Connection between Inflammation and Cardiovascular Disease

About the Author:

MPI Research, with global headquarters in Mattawan, Mich., provides safety evaluation, discovery, bioanalytical and analytical services to the biopharmaceutical, medical device, animal health, and chemical industries. The company offers comprehensive imaging solutions including preclinical imaging, radiochemistry, and data analysis. Scientific knowledge and experience, responsiveness, integrity, trust, teamwork, and dedication to strong and enduring Sponsor relationships are the defining attributes that characterize MPI Research as a high-performance, high-quality organization that is committed to bringing safer and more effective products to the world.