RT Book, Section
A1 Badimon, Lina
A1 Mendieta, Guiomar
A1 Padro, Teresa
A1 Vilahur, Gemma
A2 Kaushansky, Kenneth
A2 Prchal, Josef T.
A2 Burns, Linda J.
A2 Lichtman, Marshall A.
A2 Levi, Marcel
A2 Linch, David C.
SR Print(0)
ID 1180470794
T1 Atherothrombosis: Disease Initiation, Progression, and Treatment
T2 Williams Hematology, 10e
YR 2021
FD 2021
PB McGraw-Hill Education
PP New York, NY
SN 9781260464122
LK hemonc.mhmedical.com/content.aspx?aid=1180470794
RD 2024/04/25
AB SUMMARYComplex  cellular  and  molecular  interactions  drive  the  process  of  atherothrombosis  that  results  from  a  prolonged  course  of  different  interactions,  activations,  and  passivations  along  variable  periods  of  time.  Initially,  the  process  is  clinically  silent  (subclinical  atherosclerosis)  and  becomes  fully  apparent  when  the  atherosclerotic  process  is  complicated  with  thrombosis  and  clinical  events  are  initiated.  Atherosclerosis  is  the  main  underlying  cause  of  coronary  artery  disease,  peripheral  artery  disease,  and  cerebrovascular  disease.  Cardiovascular  risk  factors  act  as  accelerators  of  a  process  initiated  by  endothelial  dysfunction,  with  consequent  permeability  alterations,  induction  of  cytokine  expression,  loss  of  resistance  against  thrombocyte  deposition,  and  impaired  release  of  profibrinolytic  products.  A  dysfunctional  endothelium  located  in  hemodynamically  or  rheologic  compromised  areas  promotes  the  internalization  of  lipids  that  accumulate  in  the  intimal  layer  and  attract  innate  immune  cells  (eg,  monocytes)  that  become  activated  and,  by  the  local  exposure  of  modified  protein  epitopes,  damage-associated  molecular  patterns  (DAMPs),  and  oxidized  lipids  species,  initiate  the  second  phase  of  atherogenesis,  with  mild  structural  modifications  of  the  arterial  wall.  The  process  progresses  with  the  participation  of  dendritic  cells;  adaptive  immune  cells;  local  inflammation;  vascular  smooth  muscle  cell  (VSMC)  activation;  extracellular  matrix  degradation;  and  cell  apoptosis,  senescence,  and  necrosis,  and,  ultimately,  the  vascular  wall  undergoes  significant  structural  modifications  with  a  decline  in  VSMCs  and  presence  of  fragile  or  hemorrhagic  neovessels  and  calcified  nodules.  These  plaques  usually  protrude  into  the  lumen  and  are  prone  to  rupture.  Disruption  of  atherosclerotic  lesions  exposes  thrombogenic  surfaces  rich  in  tissue  factor  and  matrix  proteins  that  induce  fibrin  deposition  and  platelet  adhesion,  activation,  and  aggregation.  The  resulting  thrombi  can  be  mural  or  occlusive  depending  on  different  factors  that  are  not  fully  known.  These  thrombi  can  induce  homing  of  leucocytes  and  even  progenitor  cells.  Released  extracellular  vesicles  (mainly  microvesicles),  earlier  considered  to  be  mere  biomarkers  of  the  event,  have  been  found  to  have  a  significant  role  in  cellular  crosstalk  and  transference  of  cellular  material  in  a  paracrine  fashion.  This  chapter  reviews  our  current  understanding  of  the  pathophysiological  mechanisms  involved  in  atherothrombosis  and  analyzes  how  this  process  may  be  prevented  and  modulated.