Atherosclerosis and heart
● Atherosclerosis: complications aneurysm/dissection
○ Normal artery
■ Intima; layer of endothelial cells
■ Media; smooth muscle cells, and elastin (aorta)
■ Adventitia; fat and blood vessels
○ Atherosclerosis
■ Increased intima with inflammation and ceroid (= lipids, brown:
antibody detect in macrophages, phagocytosis of lipids.)
■ Decreased media with inflammation
■ Fibrous adventitia with inflammation
○ Aneurysm
■ Strong atherosclerosis, dilatation of the aorta
■ Major complication of an aneurysm, rupture of vessel wall
○ Dissection
■ Splicing of vessel wall, caused by
● Perforation in an atherosclerotic plaque
● Bleeding within the vessel wall, hematoma (can be
independent of atherosclerosis)
○ Age-dependent degeneration of aorta
■ Mucoid media degeneration
● Loss of elastic fibers (black); less elastic aorta
● Mucoid depositions (glycosaminoglycans); weakening of media
● Can play a role in aneurysm development and dissection
○ Genetically caused degeneration of aorta
■ Disease of fibrillin (stabilizes elastin) or collagen
■ Can play a role in aneurysm development and dissection
● Marfan disease: thin and fragmented elastin
● Ehlers-Danlos: malformation collagen with a strong variation in
collagen fiber diameter
● Valve disease: infectious/non-infectious
○ Especially aortic valve and mitral valve
○ Degeneration= thickening of the valve with fibrosis and inflammation
○ Atherosclerosis= degeneration plus ceroid/calcification
○ CRP/sPLA2-IIA and complement are more increased in atherosclerotic
compared with degenerated valves
○ Development of infectious endocarditis: mainly caused by a bacterial
infection:
■ Thrombosis of the valve
■ Necrosis of the valve
● Acute myocardial infarction: causes and complications (atherosclerosis
coronary artery)
■ Causes:
● Atherosclerosis coronary artery with unstable plaques/thrombi;
plaque rupture; plaque bleeding; dissection coronary artery;
○ Stable atherosclerotic plaque: thick fibrous cap without
inflammation in the cap
, ○ Unstable atherosclerotic plaque: thin or thick fibrous
cap with inflammation in the cap
○ Thrombus caused by:
■ Rupture of atherosclerotic plaque
■ Inflammation at the lumenal side of the coronary
artery. disruption of endothelial cells
● Myocardial bridging; vasospasm coronary artery; hypertension
related changes vasculature;
○ Large epicardial coronary artery is on the inside the
myocardium, which should be on the outside
■ Compression lumen (1) in systole (contraction
of the heart)
■ Dilatation in diastole (filling of the heart) is
inhibited (2) related to fibrosis surrounding the
vessel. (3) increased intima of coronary artery
● Small vessel disease (thickness basal membrane >1000 mm
instead of 70-80 mm, not genetically caused but diabetes II,
cocaine or developmental)
■ Findings in heart
● Calcium related deposits in mitochondria: signs of cell damage
● Detectable with loss of NBT 2-3 hours after AMI (should stain
purple with LDH)
○ 6-12 h after AMI, first inflammatory cells, neutrophilic
granulocytes
○ 12h-3 days after AMI, huge increase neutrophilic
granulocytes
○ 3-5 days after AMI, disruption neutrophilic
granulocytes, huge cardiomyocyte necrosis
○ 1-2 weeks, granulation tissue:
lymphocytes/macrophages/fibroblasts
■ Complications: death, arrhythmia (partly related with fibrosis),
pericarditis (2-3 days post-AMI: inflammation and/or thrombosis),
rupture papillary muscle; heart failure; aneurysm heart (thinning
ventricle wall); ruptured heart wall (tamponade); pericarditis
● Stenosis grades
○ Grade 1 < 25% stenosis
○ Grade 2 25-50% stenosis
○ Grade 3 50-75% stenosis
○ Grade 4 > 75% stenosis
■ Intervention
● Drugs therapy
○ Thrombolysis
● Minimally invasive
○ Stent
● Surgical
○ Bypass operation (one stenosis use an artery, more
stenosis use veins, but cannot easily handle pressure
so use fibrin glue)
, ○ Research myocardial infarction:
■ Flip-flop of the plasma membrane of cardiomyocytes facilitates post-
MI inflammation and thus increases the infarction area in days after
AMI
■ Flip-flop=translocation of negative loaded phospholipids to the outer
membrane, f.i. PS: this can be detected by AnnexinV
■ Acute phase proteins (sPLA2-IIA, CRP, complement): bind to the flip-
flopped membrane (sPLA2-IIA forms binding/activation site for CRP)
● Chemotactic (neutrophils)
● Cell damage plasma membrane
■ PX-18: prevents flip-flop and inhibits PLA2-IIA: inhibition post-MI
inflammation
○ Research venous bypass graft:
■ Arterial pressure causes distension of the vein graft when placed on
the heart
■ An elastic external stent can prevent this distension
● Myocarditis: infectious/non-infectious
■ Inflammation of the heart: infectious or non-infectious (lungemboli/
brain injury/sepsis)
■ In infectious myocarditis the predominant inflammatory cell points to
the cause; lymphocytic myocarditis,viral infection, can cause
● Arrhythmia
● Vasospasm (=contraction of blood vessels): this can cause
myocardial infarction
● Heart failure: probably related interleukins that have a negative
effect on contractility
● NOTABLY: in LM is cell death of cardiomyocytes limited,
unless a patient has a fulminant myocarditis: then there is
extensive cell death of cardiomyocyte
■ Neutrophilic granulocytes: fungi or bacteria
● Bacteria, aggregation of neutrophilic granulocytes in the heart
(in AMI a diffused increase of neutrophilic granulocytes)
■ Eosinophilic granulocytes: (without myocytolysis)
● Parasites (=infectious)
● Drug induced
■ Eosinophilic granulocytes: (with myocytolysis)
● Hypereosinophilic syndrome: systemic increase of eosinophils
in the blood
■ Granuloma: aggregates of macrophages:
● Tuberculosis
● Sarcoidosis (no necrosis of cardiomyocytes)
● Giant cell myocarditis (limited granuloma’s; extensive necrosis
of cardiomyocytes): poor prognosis
■ Stress myocarditis (non-infectious)
● Diffuse increase of neutrophilic granulocytes + lymphocytes +
macrophages
● Causes:
○ Pheochromocytoma (tumour adrenal glands)
● Atherosclerosis: complications aneurysm/dissection
○ Normal artery
■ Intima; layer of endothelial cells
■ Media; smooth muscle cells, and elastin (aorta)
■ Adventitia; fat and blood vessels
○ Atherosclerosis
■ Increased intima with inflammation and ceroid (= lipids, brown:
antibody detect in macrophages, phagocytosis of lipids.)
■ Decreased media with inflammation
■ Fibrous adventitia with inflammation
○ Aneurysm
■ Strong atherosclerosis, dilatation of the aorta
■ Major complication of an aneurysm, rupture of vessel wall
○ Dissection
■ Splicing of vessel wall, caused by
● Perforation in an atherosclerotic plaque
● Bleeding within the vessel wall, hematoma (can be
independent of atherosclerosis)
○ Age-dependent degeneration of aorta
■ Mucoid media degeneration
● Loss of elastic fibers (black); less elastic aorta
● Mucoid depositions (glycosaminoglycans); weakening of media
● Can play a role in aneurysm development and dissection
○ Genetically caused degeneration of aorta
■ Disease of fibrillin (stabilizes elastin) or collagen
■ Can play a role in aneurysm development and dissection
● Marfan disease: thin and fragmented elastin
● Ehlers-Danlos: malformation collagen with a strong variation in
collagen fiber diameter
● Valve disease: infectious/non-infectious
○ Especially aortic valve and mitral valve
○ Degeneration= thickening of the valve with fibrosis and inflammation
○ Atherosclerosis= degeneration plus ceroid/calcification
○ CRP/sPLA2-IIA and complement are more increased in atherosclerotic
compared with degenerated valves
○ Development of infectious endocarditis: mainly caused by a bacterial
infection:
■ Thrombosis of the valve
■ Necrosis of the valve
● Acute myocardial infarction: causes and complications (atherosclerosis
coronary artery)
■ Causes:
● Atherosclerosis coronary artery with unstable plaques/thrombi;
plaque rupture; plaque bleeding; dissection coronary artery;
○ Stable atherosclerotic plaque: thick fibrous cap without
inflammation in the cap
, ○ Unstable atherosclerotic plaque: thin or thick fibrous
cap with inflammation in the cap
○ Thrombus caused by:
■ Rupture of atherosclerotic plaque
■ Inflammation at the lumenal side of the coronary
artery. disruption of endothelial cells
● Myocardial bridging; vasospasm coronary artery; hypertension
related changes vasculature;
○ Large epicardial coronary artery is on the inside the
myocardium, which should be on the outside
■ Compression lumen (1) in systole (contraction
of the heart)
■ Dilatation in diastole (filling of the heart) is
inhibited (2) related to fibrosis surrounding the
vessel. (3) increased intima of coronary artery
● Small vessel disease (thickness basal membrane >1000 mm
instead of 70-80 mm, not genetically caused but diabetes II,
cocaine or developmental)
■ Findings in heart
● Calcium related deposits in mitochondria: signs of cell damage
● Detectable with loss of NBT 2-3 hours after AMI (should stain
purple with LDH)
○ 6-12 h after AMI, first inflammatory cells, neutrophilic
granulocytes
○ 12h-3 days after AMI, huge increase neutrophilic
granulocytes
○ 3-5 days after AMI, disruption neutrophilic
granulocytes, huge cardiomyocyte necrosis
○ 1-2 weeks, granulation tissue:
lymphocytes/macrophages/fibroblasts
■ Complications: death, arrhythmia (partly related with fibrosis),
pericarditis (2-3 days post-AMI: inflammation and/or thrombosis),
rupture papillary muscle; heart failure; aneurysm heart (thinning
ventricle wall); ruptured heart wall (tamponade); pericarditis
● Stenosis grades
○ Grade 1 < 25% stenosis
○ Grade 2 25-50% stenosis
○ Grade 3 50-75% stenosis
○ Grade 4 > 75% stenosis
■ Intervention
● Drugs therapy
○ Thrombolysis
● Minimally invasive
○ Stent
● Surgical
○ Bypass operation (one stenosis use an artery, more
stenosis use veins, but cannot easily handle pressure
so use fibrin glue)
, ○ Research myocardial infarction:
■ Flip-flop of the plasma membrane of cardiomyocytes facilitates post-
MI inflammation and thus increases the infarction area in days after
AMI
■ Flip-flop=translocation of negative loaded phospholipids to the outer
membrane, f.i. PS: this can be detected by AnnexinV
■ Acute phase proteins (sPLA2-IIA, CRP, complement): bind to the flip-
flopped membrane (sPLA2-IIA forms binding/activation site for CRP)
● Chemotactic (neutrophils)
● Cell damage plasma membrane
■ PX-18: prevents flip-flop and inhibits PLA2-IIA: inhibition post-MI
inflammation
○ Research venous bypass graft:
■ Arterial pressure causes distension of the vein graft when placed on
the heart
■ An elastic external stent can prevent this distension
● Myocarditis: infectious/non-infectious
■ Inflammation of the heart: infectious or non-infectious (lungemboli/
brain injury/sepsis)
■ In infectious myocarditis the predominant inflammatory cell points to
the cause; lymphocytic myocarditis,viral infection, can cause
● Arrhythmia
● Vasospasm (=contraction of blood vessels): this can cause
myocardial infarction
● Heart failure: probably related interleukins that have a negative
effect on contractility
● NOTABLY: in LM is cell death of cardiomyocytes limited,
unless a patient has a fulminant myocarditis: then there is
extensive cell death of cardiomyocyte
■ Neutrophilic granulocytes: fungi or bacteria
● Bacteria, aggregation of neutrophilic granulocytes in the heart
(in AMI a diffused increase of neutrophilic granulocytes)
■ Eosinophilic granulocytes: (without myocytolysis)
● Parasites (=infectious)
● Drug induced
■ Eosinophilic granulocytes: (with myocytolysis)
● Hypereosinophilic syndrome: systemic increase of eosinophils
in the blood
■ Granuloma: aggregates of macrophages:
● Tuberculosis
● Sarcoidosis (no necrosis of cardiomyocytes)
● Giant cell myocarditis (limited granuloma’s; extensive necrosis
of cardiomyocytes): poor prognosis
■ Stress myocarditis (non-infectious)
● Diffuse increase of neutrophilic granulocytes + lymphocytes +
macrophages
● Causes:
○ Pheochromocytoma (tumour adrenal glands)
