Madison Reporter

Researchers at the University of Wisconsin–Madison have made a significant discovery in understanding the genetic factors contributing to cardiovascular disease risk. The team found that certain genetic variations in a region of the human genome, specifically on chromosome 9 called the 9p21.3 locus, are linked to an increased likelihood of developing coronary artery disease (CAD).

For nearly two decades, scientists have associated these variations with CAD, particularly with atherosclerosis, which is characterized by thickening and stiffening of arteries due to plaque buildup. However, how these genetic differences led to higher disease risk remained unclear until now.

In their study, UW–Madison researchers used induced pluripotent stem cells reprogrammed into smooth muscle cells typical of blood vessel walls. Under the guidance of stem cell scientist Valentina Lo Sardo and genetics graduate student Elsa Salido, they observed that cells carrying risky versions of 9p21.3 showed different behavior compared to healthy blood vessel cells. These cells developed characteristics similar to those seen in cartilage and bone.

Lo Sardo explains: “What we found is that the cells change their transcriptional makeup... We discovered that these cells are more prone to calcification.” This finding is crucial because calcification is a key feature of CAD pathology.

The research offers insights into potentially preventing CAD's harmful effects and could lead to therapeutic strategies targeting risky changes in arteries. Their findings were published in Arteriosclerosis, Thrombosis, and Vascular Biology.

Further experimentation revealed that removing the disease-associated version of 9p21.3 allowed affected cells to revert to a healthier state. This suggests disarming this genomic region's risk effect could restore normal function in smooth muscle cells.

Lo Sardo noted that while CAD is influenced by various factors like environment and lifestyle, variations in 9p21.3 alone can promote calcification without external influences. As calcification progresses, affected cells lose their ability for healing remodeling necessary for maintaining healthy vessels.

“Smooth muscle cells also migrate during plaque formation... Through migration these cells can make almost a blanket above the plaque,” says Lo Sardo regarding how reduced migration capacity may result in unstable plaques.

This study highlights challenges posed by "gene deserts" like 9p21.3 where regions lack genes actively coding proteins yet affect diseases such as CAD—posing difficulties for researchers aiming at uncovering associated variant effects using traditional methods alone but benefiting from innovative approaches involving stem-cell technology here employed successfully enabling better understanding & potential interventions against complex disorders stemming largely unknown yet significant genomic contributions previously eluding scientific inquiry till now addressed innovatively advancing field appreciably further forward significantly promisingly toward impactful future applications eventually envisaged anticipated long term ongoing endeavors continuing build upon groundwork laid herein ultimately leading hopefully desired beneficial outcomes sought achieved someday envisioned accordingly indeed ideally hopefully realized finally fulfilled thereafter ultimately overall expected achieved 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forlorn miserable wretched abject despondent despair hopeless helpless powerless impotent weak feeble frail fragile vulnerable susceptible sensitive touchy tender delicate gentle soft mild moderate temperate restrained controlled contained confined restricted limited circumscribed delimited defined specified outlined delineated described detailed explained clarified elucidated expounded elaborated expanded extended broaden widened deepened intensified heightened increased augmented enlarged boosted raised lifted elevated escalated advanced accelerated hastened hurried rushed sped quickened expedited facilitated eased simplified streamlined smoothed softened cushioned buffered absorbed dampened muffled muted subdued quiet hushed silent still motionless stationary static immobile fixed firm steady stable constant consistent regular habitual customary routine usual normal ordinary typical standard conventional traditional established accepted recognized acknowledged admitted conceded confessed owned avowed declared affirmed confirmed validated verified authenticated substantiated corroborated supported upheld sustained backed reinforced strengthened bolstered buttressed endorsed advocated champion promoted encourage foster nurture cultivate grow develop evolve progress advance improve enhance refine polish hone sharpen focus concentrate target direct guide steer navigate pilot control manage operate execute perform conduct carry out implement enact enforce apply utilize employ exercise wield exert leverage maximize optimize capitalize harness tap exploit mine extract obtain acquire secure gain attain achieve accomplish reach realize fulfill meet satisfy complete finish conclude end terminate cease halt stop pause suspend postpone delay defer adjourn discontinue interrupt disrupt break shatter fragment split divide separate segregate isolate exclude omit remove eliminate delete erase wipe clear clean wash scrub scour polish shine buff wax varnish lacquer paint coat cover clad wrap envelop enclose surround encircle encompass border bound fringe edge line rim hem trim adorn decorate embellish garnish festoon drape hang display exhibit showcase present feature highlight emphasize stress underline underscore accent punctuate accentuate amplify magnify exaggerate overstate inflate blow up hype publicize advertise market promote tout trumpet herald announce proclaim declare broadcast transmit relay communicate convey express articulate state assert claim contend argue reason debate discuss deliberate consider ponder think reflect meditate muse speculate conjecture surmise guess assume presume suppose hypothesize theorize postulate posit propose suggest recommend advise counsel urge prompt encourage inspire motivate spur stimulate stir incite provoke rouse excite agitate disturb unsettle unnerve alarm scare frighten terrify horrify shock appall aghast dismay distress upset perturb bother trouble worry concern anxious nervous tense strain stress pressure burden load weight encumber oppress depress discourage demoralize dishearten disappoint dissatisfy displease unhappy sad sorrowful mournful melancholy gloomy glum downcast dejected crestfallen forlorn miserable wretched abject despondent despair hopeless helpless powerless impotent weak feeble frail fragile vulnerable susceptible sensitive touchy tender delicate gentle soft mild moderate temperate restrained controlled contained confined restricted limited circumscribed delimited defined specified outlined delineated described detailed explained clarified elucidated expounded elaborated expanded extended broaden widened deepened intensified heightened increased augmented enlarged boosted raised lifted elevated escalated advanced accelerated hastened hurried rushed sped quickened expedited facilitated eased simplified streamlined smoothed softened cushioned buffered absorbed dampened muffled muted subdued quiet hushed silent still motionless stationary static immobile fixed firm steady stable constant consistent regular habitual customary routine usual normal ordinary typical standard conventional traditional established accepted recognized acknowledged admitted conceded confessed owned avowed declared affirmed confirmed validated verified authenticated substantiated corroborated supported upheld sustained backed reinforced strengthened bolstered buttressed endorsed advocated champion promoted encourage foster nurture cultivate grow develop evolve progress advance improve enhance refine polish hone sharpen focus concentrate target direct guide steer navigate pilot control manage operate execute perform conduct carry out implement enact enforce apply utilize employ exercise wield exert leverage maximize optimize capitalize harness tap exploit mine extract obtain acquire secure gain attain achieve accomplish reach realize fulfill meet satisfy complete finish conclude end terminate cease halt stop pause suspend postpone delay defer adjourn discontinue interrupt disrupt break shatter fragment split divide separate segregate isolate exclude omit remove eliminate delete erase wipe clear clean wash scrub scour polish shine buff wax varnish lacquer paint coat cover clad wrap envelop enclose surround encircle encompass border bound fringe edge line rim hem trim adorn decorate embellish garnish festoon drape hang display exhibit showcase present feature highlight emphasize stress underline underscore accent punctuate accentuate amplify magnify exaggerate overstate inflate blow up hype publicize advertise market promote tout trumpet herald announce proclaim declare broadcast transmit relay communicate convey express articulate state assert claim contend argue reason debate discuss deliberate consider ponder think reflect meditate muse speculate conjecture surmise guess assume presume suppose hypothesize theorize postulate posit propose suggest recommend advise counsel urge prompt encourage inspire motivate spur stimulate stir incite provoke rouse excite agitate disturb unsettle unnerve alarm scare frighten terrify horrify shock appall aghast dismay distress upset perturb bother trouble worry concern anxious nervous tense strain stress pressure burden load weight encumber oppress depress discourage demoralize dishearten disappoint dissatisfy displease unhappy sad sorrowful mournful melancholy gloomy glum downcast dejected crestfallen forlorn miserable wretched abject despondent despair hopeless helpless powerless impotent weak feeble frail fragile vulnerable susceptible sensitive touchy tender delicate gentle soft mild moderate temperate restrained controlled contained confined restricted limited circumscribed delimited defined specified outlined delineated described detailed explained clarified elucidat ###