ATHEROSCLEROSIS UPDATE
ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society/Societe canadienne d'atherosclerose
Atherosclerosis and the lung David Langleben, MD, FRCPC L ong after significant atherosclerosis has developed in the systemic circulation the pulmonary arteries remain relatively clear. Mild atherosclerosis is said to be common with advanced age,'2 but yellow (presumably "fatty") streaks have been noted in pulmonary arteries of healthy 40-year-olds,3 mainly at branching points of the trunk, main and large intrapulmonary arteries,4 presumably at sites of shear stress. These early lesions do not impede pulmonary blood flow. Advanced pulmonary atherosclerosis is histologically similar to systemic atherosclerosis. It can affect arteries as small as 300 to 500 ,um. Narrowing of large arteries may be severe.5 Calcification develops and when severe may be detected radiologically. Why is the pulmonary bed relatively spared? There have been no studies of the effects of diabetes on atherogenesis in the pulmonary circulation. Smoking causes intimal abnormalities in pulmonary arteries,6 but its relation to pulmonary atherosclerosis has not been examined. The lung, which has lipoprotein lipase activity, may alter blood lipid levels, so the lipid content of pulmonary artery and aortic blood could be different. No studies have examined whether precocious systemic atherosclerosis from hyperlipidemia is associated with more advanced pulmonary atherosclerosis. The main pulmonary artery normally receives the same cardiac output as the aorta. However, high pulmonary flow, as with large intracardiac shunts, causes deep ridging of the endothelial surface of smaller pulmonary arteries and pulmonary hypertension.7 In larger proximal vessels the altered flow could increase shear stress for platelets and macrophages, which are thought to participate in atherogenesis. Pressure is the major element. Accelerated pulmonary atherosclerosis-occurs in all types of pulmonary hypertension. 1-3 Normally pulmonary artery pressure (30/12 mm Hg) is much lower than systemic
pressure because of the lower pulmonary vascular resistance. This results in less shear stress than in the aorta or mid-sized systemic arteries. Shear stress causes endothelial injury,8 which may initiate atherogenesis.9 Heath and colleagues'° found pulmonary atheroma in patients as young as 1 year with pulmonary hypertension. Pulmonary hypertension results from elevated vascular resistance due to nonatherosclerotic narrowing, obliteration or obstruction of distal small intrapulmonary arteries. The resultant increased wall stress in the proximal larger arteries accelerates the atherosclerotic process. Further examination of the atherosclerotic process in pulmonary hypertension should provide insight into both the vascular response to injury and atherogenesis in other vascular beds.
References 1. Thurlbeck WM: Pathology of the Lung, Thieme, New York, 1988: 708 2. Harris P, Heath D: The Human Pulmonary Circulation, Churchill Livingston, Edinburgh, 1986: 281-282 3. Brenner 0: Pathology of the vessels in the pulmonary circulation. Arch Intern Med 1935; 56: 211-237 4. Wagenvoort CA, Wagenvoort N: Pathology of Pulmonary Hypertension, Wiley, New York, 1977: 22-28 5. Ibid: 182-183 6. Fernie JM, McLean A, Lamb D: Significant intimal abnormalities in muscular pulmonary arteries of patients with early obstructive lung disease. J Clin Pathol 1988; 41: 730-733 7. Rabinovitch M, Bothwell T, Hayakawa BN et al: Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. Lab Invest 1986; 55: 632-653 8. Majno G, Zord T, Nunnari JJ et al: Intimal responses to shear stress, hypercholesterolemia, and hypertension. In Simionescu N, Simionescu M: Endothelial Cell Biology in Health and Disease, Plenum Pr, New York, 1988: 349-367 9. Ross R: Endothelial injury and atherosclerosis. Ibid: 371-384 10. Heath D, Wood EH, DuShane JW et al: The relation of age and blood pressure to atheroma in the pulmonary arteries and thoracic aorta in congenital heart disease. Lab Invest 1960; 9: 259-272
Dr. Langleben is an assistant professor in the Department of Medicine at McGill University, Montreal, and a research scholar of the Heart and Stroke Foundation of Canada.
Reprint requests to: Dr. David Langleben, Division of Cardiology, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Montreal, PQ H3T IE2 CAN MED ASSOC J 1990; 142 (2)
139
ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society/Societe canadienne d'atherosclerose
Atherosclerosis and the lung David Langleben, MD, FRCPC L ong after significant atherosclerosis has developed in the systemic circulation the pulmonary arteries remain relatively clear. Mild atherosclerosis is said to be common with advanced age,'2 but yellow (presumably "fatty") streaks have been noted in pulmonary arteries of healthy 40-year-olds,3 mainly at branching points of the trunk, main and large intrapulmonary arteries,4 presumably at sites of shear stress. These early lesions do not impede pulmonary blood flow. Advanced pulmonary atherosclerosis is histologically similar to systemic atherosclerosis. It can affect arteries as small as 300 to 500 ,um. Narrowing of large arteries may be severe.5 Calcification develops and when severe may be detected radiologically. Why is the pulmonary bed relatively spared? There have been no studies of the effects of diabetes on atherogenesis in the pulmonary circulation. Smoking causes intimal abnormalities in pulmonary arteries,6 but its relation to pulmonary atherosclerosis has not been examined. The lung, which has lipoprotein lipase activity, may alter blood lipid levels, so the lipid content of pulmonary artery and aortic blood could be different. No studies have examined whether precocious systemic atherosclerosis from hyperlipidemia is associated with more advanced pulmonary atherosclerosis. The main pulmonary artery normally receives the same cardiac output as the aorta. However, high pulmonary flow, as with large intracardiac shunts, causes deep ridging of the endothelial surface of smaller pulmonary arteries and pulmonary hypertension.7 In larger proximal vessels the altered flow could increase shear stress for platelets and macrophages, which are thought to participate in atherogenesis. Pressure is the major element. Accelerated pulmonary atherosclerosis-occurs in all types of pulmonary hypertension. 1-3 Normally pulmonary artery pressure (30/12 mm Hg) is much lower than systemic
pressure because of the lower pulmonary vascular resistance. This results in less shear stress than in the aorta or mid-sized systemic arteries. Shear stress causes endothelial injury,8 which may initiate atherogenesis.9 Heath and colleagues'° found pulmonary atheroma in patients as young as 1 year with pulmonary hypertension. Pulmonary hypertension results from elevated vascular resistance due to nonatherosclerotic narrowing, obliteration or obstruction of distal small intrapulmonary arteries. The resultant increased wall stress in the proximal larger arteries accelerates the atherosclerotic process. Further examination of the atherosclerotic process in pulmonary hypertension should provide insight into both the vascular response to injury and atherogenesis in other vascular beds.
References 1. Thurlbeck WM: Pathology of the Lung, Thieme, New York, 1988: 708 2. Harris P, Heath D: The Human Pulmonary Circulation, Churchill Livingston, Edinburgh, 1986: 281-282 3. Brenner 0: Pathology of the vessels in the pulmonary circulation. Arch Intern Med 1935; 56: 211-237 4. Wagenvoort CA, Wagenvoort N: Pathology of Pulmonary Hypertension, Wiley, New York, 1977: 22-28 5. Ibid: 182-183 6. Fernie JM, McLean A, Lamb D: Significant intimal abnormalities in muscular pulmonary arteries of patients with early obstructive lung disease. J Clin Pathol 1988; 41: 730-733 7. Rabinovitch M, Bothwell T, Hayakawa BN et al: Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. Lab Invest 1986; 55: 632-653 8. Majno G, Zord T, Nunnari JJ et al: Intimal responses to shear stress, hypercholesterolemia, and hypertension. In Simionescu N, Simionescu M: Endothelial Cell Biology in Health and Disease, Plenum Pr, New York, 1988: 349-367 9. Ross R: Endothelial injury and atherosclerosis. Ibid: 371-384 10. Heath D, Wood EH, DuShane JW et al: The relation of age and blood pressure to atheroma in the pulmonary arteries and thoracic aorta in congenital heart disease. Lab Invest 1960; 9: 259-272
Dr. Langleben is an assistant professor in the Department of Medicine at McGill University, Montreal, and a research scholar of the Heart and Stroke Foundation of Canada.
Reprint requests to: Dr. David Langleben, Division of Cardiology, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Montreal, PQ H3T IE2 CAN MED ASSOC J 1990; 142 (2)
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